100 years of drosophila research and its impact on vertebrate neuroscience: a history lesson for the future

ABSTRACT Discoveries in fruit flies have greatly contributed to our understanding of neuroscience. The use of an unparalleled wealth of tools, many of which originated between 1910–1960, has

enabled milestone discoveries in nervous system development and function. Such findings have triggered and guided many research efforts in vertebrate neuroscience. After 100 years, fruit

flies continue to be the choice model system for many neuroscientists. The combinational use of powerful research tools will ensure that this model organism will continue to lead to key

discoveries that will impact vertebrate neuroscience. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS

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institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Morgan, T. H. Sex limited inheritance in _Drosophila_. _Science_ 32, 120–122 (1910). CAS  PubMed  Google

Scholar  * Sturtevant, A. H. _A History of Genetics_ (Cold Spring Harbor Laboratory Press, New York, 1966). Google Scholar  * Morgan, T. H. & Bridges, C. B. Sex-linked inheritance in

_Drosophila_. _Carnegie Institute of Washington Publication_ 237, 1–88 (1916). Google Scholar  * Poulson, D. F. _Histogenesis, organogenesis and differentiation in the embryo of Drosophila

melanogaster_. (ed. Demerec, M.) (Hafner Publishing Co Ltd, Wiley, New York, 1950). Google Scholar  * Campos-Ortega, J. A. Cellular interactions during early neurogenesis of _Drosophila

melanogaster_. _Trends Neurosci._ 11, 400–405 (1988). CAS  PubMed  Google Scholar  * Wharton, K. A., Johansen, K. M., Xu, T. & Artavanis-Tsakonas, S. Nucleotide sequence from the

neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats. _Cell_ 43, 567–581 (1985). CAS  PubMed  Google Scholar  * Vassin, H., Bremer, K.

A., Knust, E. & Campos-Ortega, J. A. The neurogenic gene Delta of _Drosophila melanogaster_ is expressed in neurogenic territories and encodes a putative transmembrane protein with

EGF-like repeats. _EMBO J._ 6, 3431–3440 (1987). PubMed  PubMed Central  Google Scholar  * Artavanis-Tsakonas, S., Matsuno, K. & Fortini, M. E. Notch signaling. _Science_ 268, 225–232

(1995). CAS  PubMed  Google Scholar  * Artavanis-Tsakonas, S., Rand, M. D. & Lake, R. J. Notch signaling: cell fate control and signal integration in development. _Science_ 284, 770–776

(1999). CAS  PubMed  Google Scholar  * Ellisen, L. W. et al. TAN-1, the human homolog of the _Drosophila_ notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms.

_Cell_ 66, 649–661 (1991). CAS  PubMed  Google Scholar  * Kopan, R. & Ilagan, M. X. The canonical Notch signaling pathway: unfolding the activation mechanism. _Cell_ 137, 216–233 (2009).

CAS  PubMed  PubMed Central  Google Scholar  * Breunig, J. J., Silbereis, J., Vaccarino, F. M., Sestan, N. & Rakic, P. Notch regulates cell fate and dendrite morphology of newborn

neurons in the postnatal dentate gyrus. _Proc. Natl Acad. Sci. USA_ 104, 20558–20563 (2007). CAS  PubMed  PubMed Central  Google Scholar  * Pavlopoulos, E., Anezaki, M. & Skoulakis, E.

M. Neuralized is expressed in the alpha/beta lobes of adult _Drosophila_ mushroom bodies and facilitates olfactory long-term memory formation. _Proc. Natl Acad. Sci. USA_ 105, 14674–14679

(2008). CAS  PubMed  PubMed Central  Google Scholar  * Roca, C. & Adams, R. H. Regulation of vascular morphogenesis by Notch signaling. _Genes Dev._ 21, 2511–2524 (2007). CAS  PubMed 

Google Scholar  * Weinstein, A. Coincidence of crossing over in _Drosophila melanogaster_ (Ampelophila). _Genetics_ 3, 135–172 (1918). CAS  PubMed  PubMed Central  Google Scholar  * Bridges,

C. B. & Morgan, T. H. The third-chromosome group of mutant characters of _Drosophila melanogaster_. _Carnegie Institute of Washington Publication_ 327, 1–251 (1923). Google Scholar  *

Lewis, E. B. A gene complex controlling segmentation in _Drosophila_. _Nature_ 276, 565–570 (1978). CAS  PubMed  Google Scholar  * Sanchez-Herrero, E., Vernos, I., Marco, R. & Morata, G.

Genetic organization of _Drosophila_ bithorax complex. _Nature_ 313, 108–113 (1985). CAS  PubMed  Google Scholar  * Kaufman, T. C., Lewis, R. & Wakimoto, B. Cytogenetic analysis of

chromosome 3 in _Drosophila melanogaster_: the homoeotic gene complex in polytene chromosome interval 84a-B. _Genetics_ 94, 115–133 (1980). CAS  PubMed  PubMed Central  Google Scholar  *

Garber, R. L., Kuroiwa, A. & Gehring, W. J. Genomic and cDNA clones of the homeotic locus Antennapedia in _Drosophila_. _EMBO J._ 2, 2027–2036 (1983). CAS  PubMed  PubMed Central  Google

Scholar  * McGinnis, W., Garber, R. L., Wirz, J., Kuroiwa, A. & Gehring, W. J. A homologous protein-coding sequence in _Drosophila_ homeotic genes and its conservation in other

metazoans. _Cell_ 37, 403–408 (1984). CAS  PubMed  Google Scholar  * Duboule, D. The rise and fall of Hox gene clusters. _Development_ 134, 2549–2560 (2007). CAS  PubMed  Google Scholar  *

Alexander, T., Nolte, C. & Krumlauf, R. Hox genes and segmentation of the hindbrain and axial skeleton. _Annu. Rev. Cell Dev. Biol._ 25, 431–456 (2009). CAS  PubMed  Google Scholar  *

Dasen, J. S. & Jessell, T. M. Hox networks and the origins of motor neuron diversity. _Curr. Top. Dev. Biol._ 88, 169–200 (2009). CAS  PubMed  Google Scholar  * Dupin, E., Creuzet, S.

& Le Douarin, N. M. The contribution of the neural crest to the vertebrate body. _Adv. Exp. Med. Biol._ 589, 96–119 (2006). CAS  PubMed  Google Scholar  * Ghysen, A. &

Dambly-Chaudiere, C. From DNA to form: the achaete-scute complex. _Genes Dev._ 2, 495–501 (1988). Google Scholar  * Raffel, D. & Muller, H. J. Position effect and gene divisibility

considered in connection with three strikingly similar scute mutations. _Genetics_ 25, 541–583 (1940). CAS  PubMed  PubMed Central  Google Scholar  * Garcia-Bellido, A. & Santamaria, P.

Developmental analysis of the Achaete-Scute system of _Drosophila melanogaster_. _Genetics_ 88, 469–486 (1978). CAS  PubMed  PubMed Central  Google Scholar  * Garcia-Bellido, A. Genetic

analysis of the Achaete-Scute system of _Drosophila melanogaster_. _Genetics_ 91, 491–520 (1979). CAS  PubMed  PubMed Central  Google Scholar  * Campuzano, S. et al. Molecular genetics of

the achaete-scute gene complex of _D. melanogaster_. _Cell_ 40, 327–338 (1985). CAS  PubMed  Google Scholar  * Cabrera, C. V., Martinez-Arias, A. & Bate, M. The expression of three

members of the achaete-scute gene complex correlates with neuroblast segregation in _Drosophila_. _Cell_ 50, 425–433 (1987). CAS  PubMed  Google Scholar  * Jarman, A. P., Grau, Y., Jan, L.

Y. & Jan, Y. N. atonal is a proneural gene that directs chordotonal organ formation in the _Drosophila_ peripheral nervous system. _Cell_ 73, 1307–1321 (1993). CAS  PubMed  Google

Scholar  * Lo, L. C., Johnson, J. E., Wuenschell, C. W., Saito, T. & Anderson, D. J. Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early

neuroepithelial and neural crest cells. _Genes Dev._ 5, 1524–1537 (1991). CAS  PubMed  Google Scholar  * Bermingham, N. A. et al. Math1: an essential gene for the generation of inner ear

hair cells. _Science_ 284, 1837–1841 (1999). CAS  PubMed  Google Scholar  * Van Keymeulen, A. et al. Epidermal progenitors give rise to Merkel cells during embryonic development and adult

homeostasis. _J. Cell Biol._ 187, 91–100 (2009). CAS  PubMed  PubMed Central  Google Scholar  * Maricich, S. M. et al. Merkel cells are essential for light-touch responses. _Science_ 324,

1580–1582 (2009). CAS  PubMed  PubMed Central  Google Scholar  * Bertrand, N., Castro, D. S. & Guillemot, F. Proneural genes and the specification of neural cell types. _Nature Rev.

Neurosci._ 3, 517–530 (2002). CAS  Google Scholar  * Quan, X. J. & Hassan, B. A. From skin to nerve: flies, vertebrates and the first helix. _Cell. Mol. Life Sci._ 62, 2036–2049 (2005).

CAS  PubMed  Google Scholar  * Uemura, T., Shepherd, S., Ackerman, L., Jan, L. Y. & Jan, Y. N. numb, a gene required in determination of cell fate during sensory organ formation in

_Drosophila_ embryos. _Cell_ 58, 349–360 (1989). CAS  PubMed  Google Scholar  * Blochlinger, K., Bodmer, R., Jack, J., Jan, L. Y. & Jan, Y. N. Primary structure and expression of a

product from cut, a locus involved in specifying sensory organ identity in _Drosophila._ _Nature_ 333, 629–635 (1988). Google Scholar  * Vaessin, H. et al. prospero is expressed in neuronal

precursors and encodes a nuclear protein that is involved in the control of axonal outgrowth in _Drosophila_. _Cell_ 67, 941–953 (1991). CAS  PubMed  Google Scholar  * Nolo, R., Abbott, L.

A. & Bellen, H. J. Senseless, a Zn finger transcription factor, is necessary and sufficient for sensory organ development in _Drosophila_. _Cell_ 102, 349–362 (2000). CAS  PubMed  Google

Scholar  * Roegiers, F. & Jan, Y. N. Asymmetric cell division. _Curr. Opin. Cell Biol._ 16, 195–205 (2004). CAS  PubMed  Google Scholar  * Wallis, D. et al. The zinc finger

transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. _Development_ 130, 221–232 (2003). CAS  PubMed  Google Scholar  *

Zhong, W. & Chia, W. Neurogenesis and asymmetric cell division. _Curr. Opin. Neurobiol._ 18, 4–11 (2008). PubMed  Google Scholar  * Nusslein-Volhard, C. & Wieschaus, E. Mutations

affecting segment number and polarity in _Drosophila_. _Nature_ 287, 795–801 (1980). CAS  PubMed  Google Scholar  * Lewis, E. B., F. Bacher . Methods of feeding ethyl methane sulfonate (EMS)

to _Drosophila_ males. _Dros. Inf. Serv._ 43, 193 (1968). Google Scholar  * Jurgens, G., Wieschaus, E., Nusslein-Volhard, C. & Kluding, H. Mutations affecting the pattern of the larval

cuticle in _Drosophila melanogaster_. _Rouxs Arch. Dev. Biol._ 193, 283–295 (1984). CAS  Google Scholar  * Wieschaus, E., Nüsslein-Volhard, C. & Jürgens, G. Mutations affecting the

pattern of the larval cuticle in _Drosophila melanogaster_. _Rouxs Arch. Dev. Biol._ 193, 296–307 (1984). CAS  Google Scholar  * Ho, K. S. & Scott, M. P. Sonic hedgehog in the nervous

system: functions, modifications and mechanisms. _Curr. Opin. Neurobiol._ 12, 57–63 (2002). CAS  PubMed  Google Scholar  * Gaiano, N. Strange bedfellows: Reelin and Notch signaling interact

to regulate cell migration in the developing neocortex. _Neuron_ 60, 189–191 (2008). CAS  PubMed  Google Scholar  * Charron, F. & Tessier-Lavigne, M. The Hedgehog, TGF-β/BMP and Wnt

families of morphogens in axon guidance. _Adv. Exp. Med. Biol._ 621, 116–133 (2007). PubMed  Google Scholar  * Pozniak, C. D. & Pleasure, S. J. A tale of two signals: Wnt and Hedgehog in

dentate neurogenesis. _Sci. STKE_ 2006, pe5 (2006). * Seeger, M., Tear, G., Ferres-Marco, D. & Goodman, C. S. Mutations affecting growth cone guidance in _Drosophila_: genes necessary

for guidance toward or away from the midline. _Neuron_ 10, 409–426 (1993). CAS  PubMed  Google Scholar  * Dickson, B. J. & Gilestro, G. F. Regulation of commissural axon pathfinding by

slit and its Robo receptors. _Annu. Rev. Cell Dev. Biol._ 22, 651–675 (2006). CAS  PubMed  Google Scholar  * Kolodkin, A. L., Matthes, D. J. & Goodman, C. S. The semaphorin genes encode

a family of transmembrane and secreted growth cone guidance molecules. _Cell_ 75, 1389–1399 (1993). CAS  PubMed  Google Scholar  * Luo, Y., Raible, D. & Raper, J. A. Collapsin: a protein

in brain that induces the collapse and paralysis of neuronal growth cones. _Cell_ 75, 217–227 (1993). CAS  PubMed  Google Scholar  * Eichmann, A., Le Noble, F., Autiero, M. & Carmeliet,

P. Guidance of vascular and neural network formation. _Curr. Opin. Neurobiol._ 15, 108–115 (2005). CAS  PubMed  Google Scholar  * Benzer, S. Behavioral mutants of _Drosophila_ isolated by

countercurrent distribution. _Proc. Natl Acad. Sci. USA_ 58, 1112–1119 (1967). CAS  PubMed  PubMed Central  Google Scholar  * Konopka, R. J. & Benzer, S. Clock mutants of _Drosophila

melanogaster_. _Proc. Natl Acad. Sci. USA_ 68, 2112–2116 (1971). CAS  PubMed  PubMed Central  Google Scholar  * Bargiello, T. A., Jackson, F. R. & Young, M. W. Restoration of circadian

behavioural rhythms by gene transfer in _Drosophila_. _Nature_ 312, 752–754 (1984). CAS  PubMed  Google Scholar  * Reddy, P. et al. Molecular analysis of the period locus in _Drosophila

melanogaster_ and identification of a transcript involved in biological rhythms. _Cell_ 38, 701–710 (1984). CAS  PubMed  Google Scholar  * Zehring, W. A. et al. P-element transformation with

period locus DNA restores rhythmicity to mutant, arrhythmic _Drosophila melanogaster_. _Cell_ 39, 369–376 (1984). CAS  PubMed  Google Scholar  * Bargiello, T. A. & Young, M. W.

Molecular genetics of a biological clock in _Drosophila_. _Proc. Natl Acad. Sci. USA_ 81, 2142–2146 (1984). CAS  PubMed  PubMed Central  Google Scholar  * Sun, Z. S. et al. RIGUI, a putative

mammalian ortholog of the _Drosophila_ period gene. _Cell_ 90, 1003–1011 (1997). CAS  PubMed  Google Scholar  * Sehgal, A., Price, J. L., Man, B. & Young, M. W. Loss of circadian

behavioral rhythms and per RNA oscillations in the _Drosophila_ mutant timeless. _Science_ 263, 1603–1606 (1994). CAS  PubMed  Google Scholar  * Vitaterna, M. H. et al. Mutagenesis and

mapping of a mouse gene, Clock, essential for circadian behavior. _Science_ 264, 719–725 (1994). CAS  PubMed  PubMed Central  Google Scholar  * King, D. P. et al. The mouse Clock mutation

behaves as an antimorph and maps within the W19H deletion, distal of Kit. _Genetics_ 146, 1049–1060 (1997). CAS  PubMed  PubMed Central  Google Scholar  * Takahashi, J. S., Hong, H. K., Ko,

C. H. & McDearmon, E. L. The genetics of mammalian circadian order and disorder: implications for physiology and disease. _Nature Rev. Genet._ 9, 764–775 (2008). CAS  PubMed  Google

Scholar  * Quinn, W. G., Harris, W. A. & Benzer, S. Conditioned behavior in _Drosophila melanogaster_. _Proc. Natl Acad. Sci. USA_ 71, 708–712 (1974). CAS  PubMed  PubMed Central  Google

Scholar  * Dudai, Y., Jan, Y. N., Byers, D., Quinn, W. G. & Benzer, S. dunce, a mutant of _Drosophila_ deficient in learning. _Proc. Natl Acad. Sci. USA_ 73, 1684–1688 (1976). CAS 

PubMed  PubMed Central  Google Scholar  * Byers, D., Davis, R. L. & Kiger, J. A., Jr. Defect in cyclic AMP phosphodiesterase due to the dunce mutation of learning in _Drosophila

melanogaster_. _Nature_ 289, 79–81 (1981). CAS  PubMed  Google Scholar  * Davis, R. L. & Kiger, J. A., Jr. Dunce mutants of _Drosophila melanogaster_: mutants defective in the cyclic AMP

phosphodiesterase enzyme system. _J. Cell Biol._ 90, 101–107 (1981). CAS  PubMed  Google Scholar  * Chen, C. N., Denome, S. & Davis, R. L. Molecular analysis of cDNA clones and the

corresponding genomic coding sequences of the _Drosophila_ dunce+ gene, the structural gene for cAMP phosphodiesterase. _Proc. Natl Acad. Sci. USA_ 83, 9313–9317 (1986). CAS  PubMed  PubMed

Central  Google Scholar  * Livingstone, M. S., Sziber, P. P. & Quinn, W. G. Loss of calcium/calmodulin responsiveness in adenylate cyclase of rutabaga, a _Drosophila_ learning mutant.

_Cell_ 37, 205–215 (1984). CAS  PubMed  Google Scholar  * McGuire, S. E., Deshazer, M. & Davis, R. L. Thirty years of olfactory learning and memory research in _Drosophila melanogaster_.

_Prog. Neurobiol._ 76, 328–347 (2005). CAS  PubMed  Google Scholar  * Kandel, E. R. & Schwartz, J. H. Molecular biology of learning: modulation of transmitter release. _Science_ 218,

433–443 (1982). CAS  PubMed  Google Scholar  * Alberini, C. M. Genes to remember. _J. Exp. Biol._ 202, 2887–2891 (1999). CAS  PubMed  Google Scholar  * Barco, A., Bailey, C. H. & Kandel,

E. R. Common molecular mechanisms in explicit and implicit memory. _J. Neurochem._ 97, 1520–1533 (2006). CAS  PubMed  Google Scholar  * Yu, D., Ponomarev, A. & Davis, R. L. Altered

representation of the spatial code for odors after olfactory classical conditioning; memory trace formation by synaptic recruitment. _Neuron_ 42, 437–449 (2004). CAS  PubMed  Google Scholar

  * Pak, W. L., Grossfield, J. & White, N. V. Nonphototactic mutants in a study of vision of _Drosophila_. _Nature_ 222, 351–354 (1969). CAS  PubMed  Google Scholar  * Pak, W. L.,

Grossfield, J. & Arnold, K. S. Mutants of the visual pathway of _Drosophila melanogaster_. _Nature_ 227, 518–520 (1970). CAS  PubMed  Google Scholar  * Cosens, D. J. & Manning, A.

Abnormal electroretinogram from a _Drosophila_ mutant. _Nature_ 224, 285–287 (1969). CAS  PubMed  Google Scholar  * Minke, B., Wu, C. & Pak, W. L. Induction of photoreceptor voltage

noise in the dark in _Drosophila_ mutant. _Nature_ 258, 84–87 (1975). CAS  PubMed  Google Scholar  * Zuker, C. S. The biology of vision of _Drosophila_. _Proc. Natl Acad. Sci. USA_ 93,

571–576 (1996). CAS  PubMed  PubMed Central  Google Scholar  * Levis, R., Bingham, P. M. & Rubin, G. M. Physical map of the white locus of _Drosophila melanogaster_. _Proc. Natl Acad.

Sci. USA_ 79, 564–568 (1982). CAS  PubMed  PubMed Central  Google Scholar  * Zipursky, S. L. & Rubin, G. M. Determination of neuronal cell fate: lessons from the R7 neuron of

_Drosophila_. _Annu. Rev. Neurosci._ 17, 373–397 (1994). CAS  PubMed  Google Scholar  * Rubin, G. M. & Spradling, A. C. Genetic transformation of _Drosophila_ with transposable element

vectors. _Science_ 218, 348–353 (1982). CAS  PubMed  Google Scholar  * Montell, C., Jones, K., Hafen, E. & Rubin, G. Rescue of the _Drosophila_ phototransduction mutation trp by germline

transformation. _Science_ 230, 1040–1043 (1985). CAS  PubMed  Google Scholar  * Montell, C. Visual transduction in _Drosophila_. _Annu. Rev. Cell Dev. Biol._ 15, 231–268 (1999). CAS  PubMed

  Google Scholar  * Wes, P. D. et al. TRPC1, a human homolog of a _Drosophila_ store-operated channel. _Proc. Natl Acad. Sci. USA_ 92, 9652–9656 (1995). CAS  PubMed  PubMed Central  Google

Scholar  * Venkatachalam, K. & Montell, C. TRP channels. _Annu. Rev. Biochem._ 76, 387–417 (2007). CAS  PubMed  PubMed Central  Google Scholar  * Minke, B. & Cook, B. TRP channel

proteins and signal transduction. _Physiol. Rev._ 82, 429–472 (2002). CAS  PubMed  Google Scholar  * Dong, X. P. et al. The type IV mucolipidosis-associated protein TRPML1 is an

endolysosomal iron release channel. _Nature_ 455, 992–996 (2008). CAS  PubMed  PubMed Central  Google Scholar  * Landouré, G. et al. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type

2C. _Nature Genet._ 42, 170–174 (2009). PubMed  Google Scholar  * Deng, H. X. et al. Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4.

_Nature Genet._ 42, 165–169 (2009). PubMed  Google Scholar  * Auer-Grumbach, M. et al. Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.

_Nature Genet._ 42, 160–164 (2009). PubMed  Google Scholar  * Kaplan, W. D. & Trout, W. E., 3rd. The behavior of four neurological mutants of _Drosophila_. _Genetics_ 61, 399–409

(1969). CAS  PubMed  PubMed Central  Google Scholar  * Jan, L. Y. & Jan, Y. N. Properties of the larval neuromuscular junction in _Drosophila melanogaster_. _J. Physiol._ 262, 189–214

(1976). CAS  PubMed  PubMed Central  Google Scholar  * Jan, Y. N., Jan, L. Y. & Dennis, M. J. Two mutations of synaptic transmission in _Drosophila_. _Proc. R. Soc. Lond. B Biol. Sci._

198, 87–108 (1977). CAS  PubMed  Google Scholar  * Ganetzky, B. & Wu, C. F. Indirect suppression involving behavioral mutants with altered nerve excitability in _Drosophila_ melanogster.

_Genetics_ 100, 597–614 (1982). CAS  PubMed  PubMed Central  Google Scholar  * Wu, C. F., Ganetzky, B., Haugland, F. N. & Liu, A. X. Potassium currents in _Drosophila_: different

components affected by mutations of two genes. _Science_ 220, 1076–1078 (1983). CAS  PubMed  Google Scholar  * Baumann, A. et al. Molecular organization of the maternal effect region of the

Shaker complex of _Drosophila_: characterization of an I(A) channel transcript with homology to vertebrate Na channel. _EMBO J._ 6, 3419–3429 (1987). CAS  PubMed  PubMed Central  Google

Scholar  * Kamb, A., Iverson, L. E. & Tanouye, M. A. Molecular characterization of Shaker, a _Drosophila_ gene that encodes a potassium channel. _Cell_ 50, 405–413 (1987). CAS  PubMed 

Google Scholar  * Papazian, D. M., Schwarz, T. L., Tempel, B. L., Jan, Y. N. & Jan, L. Y. Cloning of genomic and complementary DNA from Shaker, a putative potassium channel gene from

_Drosophila_. _Science_ 237, 749–753 (1987). CAS  PubMed  Google Scholar  * Tempel, B. L., Papazian, D. M., Schwarz, T. L., Jan, Y. N. & Jan, L. Y. Sequence of a probable potassium

channel component encoded at Shaker locus of _Drosophila_. _Science_ 237, 770–775 (1987). CAS  PubMed  Google Scholar  * Salkoff, L. et al. An essential 'set' of K+ channels

conserved in flies, mice and humans. _Trends Neurosci._ 15, 161–166 (1992). CAS  PubMed  Google Scholar  * Ganetzky, B. & Wu, C. F. Neurogenetic analysis of potassium currents in

_Drosophila_: synergistic effects on neuromuscular transmission in double mutants. _J. Neurogenet._ 1, 17–28 (1983). CAS  PubMed  Google Scholar  * Warmke, J., Drysdale, R. & Ganetzky,

B. A distinct potassium channel polypeptide encoded by the _Drosophila_ eag locus. _Science_ 252, 1560–1562 (1991). CAS  PubMed  Google Scholar  * Warmke, J. W. & Ganetzky, B. A family

of potassium channel genes related to eag in _Drosophila_ and mammals. _Proc. Natl Acad. Sci. USA_ 91, 3438–3442 (1994). CAS  PubMed  PubMed Central  Google Scholar  * Curran, M. E. et al. A

molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. _Cell_ 80, 795–803 (1995). CAS  PubMed  Google Scholar  * Jan, L. Y. & Jan, Y. N. Cloned potassium

channels from eukaryotes and prokaryotes. _Annu. Rev. Neurosci._ 20, 91–123 (1997). CAS  PubMed  Google Scholar  * Jentsch, T. J. Neuronal KCNQ potassium channels: physiology and role in

disease. _Nature Rev. Neurosci._ 1, 21–30 (2000). CAS  Google Scholar  * Featherstone, D. E., Chen, K. & Broadie, K. Harvesting and preparing _Drosophila_ embryos for

electrophysiological recording and other procedures. _J. Vis. Exp._ 20 May 2009 (doi: 10.3791/1347). * Brent, J., Werner, K. & McCabe, B. D. _Drosophila_ larval NMJ immunohistochemistry.

_J. Vis. Exp._ 28 March 2009 (doi: 10.3791/1108). * Bellen, H., Budnik, V. _The_ _Neuromuscular Junction_ (ed. W. Sullivan, M. A.a.R. S. H.) (Cold Spring Harbor Laboratory Press, New York,

2000). Google Scholar  * Koh, T. W. et al. Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development. _J. Cell Biol._ 178, 309–322 (2007). CAS  PubMed  PubMed

Central  Google Scholar  * Littleton, J. T., Stern, M., Perin, M. & Bellen, H. J. Calcium dependence of neurotransmitter release and rate of spontaneous vesicle fusions are altered in

_Drosophila_ synaptotagmin mutants. _Proc. Natl Acad. Sci. USA_ 91, 10888–10892 (1994). CAS  PubMed  PubMed Central  Google Scholar  * Littleton, J. T., Stern, M., Schulze, K., Perin, M.

& Bellen, H. J. Mutational analysis of _Drosophila_ synaptotagmin demonstrates its essential role in Ca(2+)-activated neurotransmitter release. _Cell_ 74, 1125–1134 (1993). CAS  PubMed 

Google Scholar  * DiAntonio, A., Parfitt, K. D. & Schwarz, T. L. Synaptic transmission persists in synaptotagmin mutants of _Drosophila_. _Cell_ 73, 1281–1290 (1993). CAS  PubMed  Google

Scholar  * Poodry, C. A., Hall, L. & Suzuki, D. T. Developmental properties of Shibire: a pleiotropic mutation affecting larval and adult locomotion and development. _Dev. Biol._ 32,

373–386 (1973). CAS  PubMed  Google Scholar  * van der Bliek, A. M. & Meyerowitz, E. M. Dynamin-like protein encoded by the _Drosophila_ shibire gene associated with vesicular traffic.

_Nature_ 351, 411–414 (1991). CAS  PubMed  Google Scholar  * Poodry, C. A. & Edgar, L. Reversible alteration in the neuromuscular junctions of _Drosophila melanogaster_ bearing a

temperature-sensitive mutation, shibire. _J. Cell Biol._ 81, 520–527 (1979). CAS  PubMed  Google Scholar  * Koenig, J. H., Kosaka, T. & Ikeda, K. The relationship between the number of

synaptic vesicles and the amount of transmitter released. _J. Neurosci._ 9, 1937–1942 (1989). CAS  PubMed  PubMed Central  Google Scholar  * Richmond, J. E. & Broadie, K. S. The synaptic

vesicle cycle: exocytosis and endocytosis in _Drosophila_ and _C. elegans_. _Curr. Opin. Neurobiol._ 12, 499–507 (2002). CAS  PubMed  Google Scholar  * Schwarz, T. L. Transmitter release at

the neuromuscular junction. _Int. Rev. Neurobiol._ 75, 105–144 (2006). CAS  PubMed  Google Scholar  * Sudhof, T. C. The synaptic vesicle cycle. _Annu. Rev. Neurosci._ 27, 509–547 (2004).

PubMed  Google Scholar  * Bellen, H. J. et al. The BDGP gene disruption project: single transposon insertions associated with 40% of _Drosophila_ genes. _Genetics_ 167, 761–781 (2004).

Google Scholar  * Venken, K. J. & Bellen, H. J. Emerging technologies for gene manipulation in _Drosophila melanogaster_. _Nature Rev. Genet._ 6, 167–178 (2005). CAS  PubMed  Google

Scholar  * Venken, K. J. & Bellen, H. J. Transgenesis upgrades for _Drosophila melanogaster_. _Development_ 134, 3571–3584 (2007). CAS  PubMed  Google Scholar  * Hobert, O. The impact of

whole genome sequencing on model system genetics: get ready for the ride. _Genetics_ 184, 317–319 (2010). CAS  PubMed  PubMed Central  Google Scholar  * Rong, Y. S. et al. Targeted

mutagenesis by homologous recombination in _D. melanogaster_. _Genes Dev._ 16, 1568–1581 (2002). CAS  PubMed  PubMed Central  Google Scholar  * Dietzl, G. et al. A genome-wide transgenic

RNAi library for conditional gene inactivation in _Drosophila_. _Nature_ 448, 151–156 (2007). CAS  PubMed  Google Scholar  * Ni, J. Q. et al. A _Drosophila_ resource of transgenic RNAi lines

for neurogenetics. _Genetics_ 182, 1089–1100 (2009). CAS  PubMed  PubMed Central  Google Scholar  * Venken, K. J., He, Y., Hoskins, R. A. & Bellen, H. J. P[acman]: a BAC transgenic

platform for targeted insertion of large DNA fragments in _D. melanogaster_. _Science_ 314, 1747–1751 (2006). CAS  PubMed  Google Scholar  * Groth, A. C. & Calos, M. P. Phage integrases:

biology and applications. _J. Mol. Biol._ 335, 667–678 (2004). CAS  PubMed  Google Scholar  * Golic, K. G. & Lindquist, S. The FLP recombinase of yeast catalyzes site-specific

recombination in the _Drosophila_ genome. _Cell_ 59, 499–509 (1989). CAS  PubMed  Google Scholar  * Golic, K. G. Site-specific recombination between homologous chromosomes in _Drosophila_.

_Science_ 252, 958–961 (1991). CAS  PubMed  Google Scholar  * Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.

_Development_ 118, 401–415 (1993). CAS  PubMed  Google Scholar  * Lee, T. & Luo, L. Mosaic analysis with a repressible cell marker (MARCM) for _Drosophila_ neural development . _Trends

Neurosci._ 24, 251–254 (2001). CAS  PubMed  Google Scholar  * Venken, K. J. et al. Versatile P[acman] BAC libraries for transgenesis studies in _Drosophila melanogaster_. _Nature Methods_ 6,

431–434 (2009). CAS  PubMed  PubMed Central  Google Scholar  * Broadie, K. & Bate, M. Activity-dependent development of the neuromuscular synapse during _Drosophila_ embryogenesis.

_Neuron_ 11, 607–619 (1993). CAS  PubMed  Google Scholar  * Broadie, K. in _Drosophila Protocols_ (eds Sullivan, W., Ashburner, M. & Hawley, S.) 273–296 (Cold Spring Harbor Laboratory

Press, Cold Spring Harbor, New York, 2000). Google Scholar  * Howlett, I. C. & Tanouye, M. A. Neurocircuit assays for seizures in epilepsy mutants of _Drosophila_. _J. Vis. Exp._ 15

April 2009 (doi: 10.3791/1121). * Nitz, D. A., van Swinderen, B., Tononi, G. & Greenspan, R. J. Electrophysiological correlates of rest and activity in _Drosophila melanogaster_. _Curr.

Biol._ 12, 1934–1940 (2002). CAS  PubMed  Google Scholar  * Gu, H. et al. Cav2-type calcium channels encoded by cac regulate AP-independent neurotransmitter release at cholinergic synapses

in adult _Drosophila_ brain. _J. Neurophysiol._ 101, 42–53 (2009). CAS  PubMed  Google Scholar  * Rohrbough, J. & Broadie, K. Electrophysiological analysis of synaptic transmission in

central neurons of _Drosophila_ larvae. _J. Neurophysiol._ 88, 847–860 (2002). PubMed  Google Scholar  * Mamiya, A., Beshel, J., Xu, C. & Zhong, Y. Neural representations of airflow in

_Drosophila_ mushroom body. _PLoS ONE_ 3, e4063 (2008). PubMed  PubMed Central  Google Scholar  * Pfeiffer, B. D. et al. Tools for neuroanatomy and neurogenetics in _Drosophila_. _Proc. Natl

Acad. Sci. USA_ 105, 9715–9720 (2008). CAS  PubMed  PubMed Central  Google Scholar  * Sweeney, S. T., Broadie, K., Keane, J., Niemann, H. & O'Kane, C. J. Targeted expression of

tetanus toxin light chain in _Drosophila_ specifically eliminates synaptic transmission and causes behavioral defects. _Neuron_ 14, 341–351 (1995). CAS  PubMed  Google Scholar  * Kitamoto,

T. Targeted expression of temperature-sensitive dynamin to study neural mechanisms of complex behavior in _Drosophila_. _J. Neurogenet._ 16, 205–228 (2002). CAS  PubMed  Google Scholar  *

Ren, D. et al. A prokaryotic voltage-gated sodium channel. _Science_ 294, 2372–2375 (2001). CAS  PubMed  Google Scholar  * Luan, H. et al. Functional dissection of a neuronal network

required for cuticle tanning and wing expansion in _Drosophila_. _J. Neurosci._ 26, 573–584 (2006). CAS  PubMed  PubMed Central  Google Scholar  * Miesenbock, G. The optogenetic catechism.

_Science_ 326, 395–399 (2009). PubMed  Google Scholar  * Shaw, P. J., Cirelli, C., Greenspan, R. J. & Tononi, G. Correlates of sleep and waking in _Drosophila melanogaster_. _Science_

287, 1834–1837 (2000). CAS  PubMed  Google Scholar  * Harbison, S. T., Mackay, T. F. & Anholt, R. R. Understanding the neurogenetics of sleep: progress from _Drosophila_. _Trends Genet._

25, 262–269 (2009). CAS  PubMed  PubMed Central  Google Scholar  * Cirelli, C. The genetic and molecular regulation of sleep: from fruit flies to humans. _Nature Rev. Neurosci._ 10, 549–560

(2009). CAS  Google Scholar  * Koh, K. et al. Identification of SLEEPLESS, a sleep-promoting factor. _Science_ 321, 372–376 (2008). CAS  PubMed  PubMed Central  Google Scholar  * Wu, M. N.

et al. SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker. _Nature Neurosci._ 13, 69–75 (2010). CAS  PubMed  Google Scholar  * Cirelli, C.

et al. Reduced sleep in _Drosophila_ Shaker mutants. _Nature_ 434, 1087–1092 (2005). CAS  PubMed  Google Scholar  * Axel, R. Scents and sensibility: a molecular logic of olfactory perception

(Nobel lecture). _Angew. Chem. Int. Ed Engl._ 44, 6110–6127 (2005). PubMed  Google Scholar  * Anderson, D. J. Profile of David J. Anderson. Interview by Kaspar D. Mossman. _Proc. Natl Acad.

Sci. USA_ 106, 17623–17625 (2009). PubMed  Google Scholar  * Lozano, A. M., Lang, A. E., Hutchison, W. D. & Dostrovsky, J. O. New developments in understanding the etiology of

Parkinson's disease and in its treatment. _Curr. Opin. Neurobiol._ 8, 783–790 (1998). CAS  PubMed  Google Scholar  * Polymeropoulos, M. H. et al. Mutation in the alpha-synuclein gene

identified in families with Parkinson's disease. _Science_ 276, 2045–2047 (1997). CAS  PubMed  Google Scholar  * Kitada, T. et al. Mutations in the parkin gene cause autosomal recessive

juvenile parkinsonism. _Nature_ 392, 605–608 (1998). CAS  PubMed  Google Scholar  * Valente, E. M. et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1.

_Science_ 304, 1158–1160 (2004). CAS  PubMed  Google Scholar  * Greene, J. C. et al. Mitochondrial pathology and apoptotic muscle degeneration in _Drosophila_ parkin mutants. _Proc. Natl

Acad. Sci. USA_ 100, 4078–4083 (2003). CAS  PubMed  PubMed Central  Google Scholar  * Pesah, Y. et al. _Drosophila_ parkin mutants have decreased mass and cell size and increased sensitivity

to oxygen radical stress. _Development_ 131, 2183–2194 (2004). CAS  PubMed  Google Scholar  * Orr, H. T. & Zoghbi, H. Y. Trinucleotide repeat disorders. _Annu. Rev. Neurosci._ 30,

575–621 (2007). CAS  PubMed  Google Scholar  * Lessing, D. & Bonini, N. M. Maintaining the brain: insight into human neurodegeneration from _Drosophila melanogaster_ mutants. _Nature

Rev. Genet._ 10, 359–370 (2009). CAS  PubMed  Google Scholar  * Botas, J. _Drosophila_ researchers focus on human disease. _Nature Genet._ 39, 589–591 (2007). CAS  PubMed  Google Scholar  *

Vosshall, L. B. & Stocker, R. F. Molecular architecture of smell and taste in _Drosophila_. _Annu. Rev. Neurosci._ 30, 505–533 (2007). CAS  PubMed  Google Scholar  * Iliadi, K. G. The

genetic basis of emotional behavior: has the time come for a _Drosophila_ model? _J. Neurogenet._ 23, 136–146 (2009). CAS  PubMed  Google Scholar  * Kernan, M. J. Mechanotransduction and

auditory transduction in _Drosophila_. _Pflugers Arch._ 454, 703–720 (2007). CAS  PubMed  Google Scholar  * Fotowat, H., Fayyazuddin, A., Bellen, H. J. & Gabbiani, F. A novel neuronal

pathway for visually guided escape in _Drosophila melanogaster_. _J. Neurophysiol._ 102, 875–885 (2009). PubMed  PubMed Central  Google Scholar  * Manoli, D. S., Meissner, G. W. & Baker,

B. S. Blueprints for behavior: genetic specification of neural circuitry for innate behaviors. _Trends Neurosci._ 29, 444–451 (2006). CAS  PubMed  Google Scholar  * Dickson, B. J. Wired for

sex: the neurobiology of _Drosophila_ mating decisions. _Science_ 322, 904–909 (2008). CAS  PubMed  Google Scholar  * Muller, H. J. Genetic variability, twin hybrids and constant hybrids,

in a case of balanced lethal factors. _Genetics_ 3, 422–499 (1918). CAS  PubMed  PubMed Central  Google Scholar  * Muller, H. J. Artificial transmutation of the gene. _Science_ 66, 84–87

(1927). CAS  PubMed  Google Scholar  * Bridges, C. B. Salivary chromosome maps with a key to the banding of the chromosomes of _Drosophila melanogaster_. _J. Hered._ 26, 60–64 (1935). Google

Scholar  * Stern, C. Somatic crossing over and segregation in _Drosophila melanogaster_. _Genetics_ 21, 625–730 (1936). CAS  PubMed  PubMed Central  Google Scholar  * Fuccillo, M., Joyner,

A. L. & Fishell, G. Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development. _Nature Rev. Neurosci._ 7, 772–783 (2006). CAS  Google Scholar  *

Kunes, S. Axonal signals in the assembly of neural circuitry. _Curr. Opin. Neurobiol._ 10, 58–62 (2000). CAS  PubMed  Google Scholar  * Doe, C. Q. Neural stem cells: balancing self-renewal

with differentiation. _Development_ 135, 1575–1587 (2008). CAS  PubMed  Google Scholar  * Ciani, L. & Salinas, P. C. WNTs in the vertebrate nervous system: from patterning to neuronal

connectivity. _Nature Rev. Neurosci._ 6, 351–362 (2005). CAS  Google Scholar  * Legent, K. & Treisman, J. E. Wingless signaling in _Drosophila_ eye development. _Methods Mol. Biol._ 469,

141–161 (2008). CAS  PubMed  PubMed Central  Google Scholar  * Inestrosa, N. C. & Arenas, E. Emerging roles of Wnts in the adult nervous system. _Nature Rev. Neurosci._ 11, 77–86

(2010). CAS  Google Scholar  * Korkut, C. & Budnik, V. WNTs tune up the neuromuscular junction. _Nature Rev. Neurosci._ 10, 627–634 (2009). CAS  Google Scholar  * Liu, A. &

Niswander, L. A. Bone morphogenetic protein signalling and vertebrate nervous system development. _Nature Rev. Neurosci._ 6, 945–954 (2005). CAS  Google Scholar  * Kaphingst, K. & Kunes,

S. Pattern formation in the visual centers of the _Drosophila_ brain: wingless acts via decapentaplegic to specify the dorsoventral axis. _Cell_ 78, 437–448 (1994). CAS  PubMed  Google

Scholar  * Yoshida, S. et al. DPP signaling controls development of the lamina glia required for retinal axon targeting in the visual system of _Drosophila_. _Development_ 132, 4587–4598

(2005). CAS  PubMed  Google Scholar  * Parker, L., Ellis, J. E., Nguyen, M. Q. & Arora, K. The divergent TGF-beta ligand Dawdle utilizes an activin pathway to influence axon guidance in

_Drosophila_. _Development_ 133, 4981–4991 (2006). CAS  PubMed  Google Scholar  * Serpe, M. & O'Connor, M. B. The metalloprotease tolloid-related and its TGF-b-like substrate Dawdle

regulate _Drosophila_ motoneuron axon guidance. _Development_ 133, 4969–4979 (2006). CAS  PubMed  Google Scholar  * Keshishian, H. & Kim, Y. S. Orchestrating development and function:

retrograde BMP signaling in the _Drosophila_ nervous system. _Trends Neurosci._ 27, 143–147 (2004). CAS  PubMed  Google Scholar  * James, D., Levine, A. J., Besser, D. &

Hemmati-Brivanlou, A. TGFb/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. _Development_ 132, 1273–1282 (2005). CAS  PubMed  Google

Scholar  * Ogawa, K. et al. Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells. _J. Cell Sci._ 120, 55–65 (2007). CAS  PubMed  Google Scholar  * Louvi, A. &

Artavanis-Tsakonas, S. Notch signalling in vertebrate neural development. _Nature Rev. Neurosci._ 7, 93–102 (2006). CAS  Google Scholar  * Bardin, A. J., Le Borgne, R. & Schweisguth, F.

Asymmetric localization and function of cell-fate determinants: a fly's view. _Curr. Opin. Neurobiol._ 14, 6–14 (2004). CAS  PubMed  Google Scholar  * Carthew, R. W. Pattern formation

in the _Drosophila_ eye. _Curr. Opin. Genet. Dev._ 17, 309–313 (2007). CAS  PubMed  PubMed Central  Google Scholar  * Le Gall, M., De Mattei, C. & Giniger, E. Molecular separation of two

signaling pathways for the receptor, Notch. _Dev. Biol._ 313, 556–567 (2008). CAS  PubMed  Google Scholar  * de Bivort, B. L., Guo, H. F. & Zhong, Y. Notch signaling is required for

activity-dependent synaptic plasticity at the _Drosophila_ neuromuscular junction. _J. Neurogenet._ 23, 395–404 (2009). PubMed  PubMed Central  Google Scholar  * Hou, J., Tamura, T. &

Kidokoro, Y. Delayed synaptic transmission in _Drosophila cacophony_ null embryos. _J. Neurophysiol._ 100, 2833–2842 (2008). PubMed  Google Scholar  * Xue, M. et al. Tilting the balance

between facilitatory and inhibitory functions of mammalian and _Drosophila_ Complexins orchestrates synaptic vesicle exocytosis. _Neuron_ 64, 367–380 (2009). CAS  PubMed  PubMed Central 

Google Scholar  * Bronk, P. et al. The multiple functions of cysteine-string protein analyzed at _Drosophila_ nerve terminals. _J. Neurosci._ 25, 2204–2214 (2005). CAS  PubMed  PubMed

Central  Google Scholar  * Ohyama, T. et al. Huntingtin-interacting protein 14, a palmitoyl transferase required for exocytosis and targeting of CSP to synaptic vesicles. _J. Cell Biol._

179, 1481–1496 (2007). CAS  PubMed  PubMed Central  Google Scholar  * Schulze, K. L. et al. rop, a _Drosophila_ homolog of yeast Sec1 and vertebrate n-Sec1/Munc-18 proteins, is a negative

regulator of neurotransmitter release _in vivo_. _Neuron_ 13, 1099–1108 (1994). CAS  PubMed  Google Scholar  * Ly, C. V., Yao, C. K., Verstreken, P., Ohyama, T. & Bellen, H. J.

straightjacket is required for the synaptic stabilization of cacophony, a voltage-gated calcium channel a1 subunit. _J. Cell Biol._ 181, 157–170 (2008). CAS  PubMed  PubMed Central  Google

Scholar  * Vilinsky, I., Stewart, B. A., Drummond, J., Robinson, I. & Deitcher, D. L. A _Drosophila SNAP-25_ null mutant reveals context-dependent redundancy with SNAP-24 in

neurotransmission. _Genetics_ 162, 259–271 (2002). CAS  PubMed  PubMed Central  Google Scholar  * Broadie, K. et al. Syntaxin and synaptobrevin function downstream of vesicle docking in

_Drosophila_. _Neuron_ 15, 663–673 (1995). CAS  PubMed  Google Scholar  * Schulze, K. L., Broadie, K., Perin, M. S. & Bellen, H. J. Genetic and electrophysiological studies of

_Drosophila_ syntaxin-1A demonstrate its role in nonneuronal secretion and neurotransmission. _Cell_ 80, 311–320 (1995). CAS  PubMed  Google Scholar  * Wu, M. N. et al. Syntaxin 1A interacts

with multiple exocytic proteins to regulate neurotransmitter release _in vivo_. _Neuron_ 23, 593–605 (1999). CAS  PubMed  Google Scholar  * Aravamudan, B., Fergestad, T., Davis, W. S.,

Rodesch, C. K. & Broadie, K. _Drosophila_ UNC-13 is essential for synaptic transmission. _Nature Neurosci._ 2, 965–971 (1999). CAS  PubMed  Google Scholar  * Hiesinger, P. R. et al. The

v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in _Drosophila_. _Cell_ 121, 607–620 (2005). CAS  PubMed  PubMed Central  Google Scholar  * Zhang, B. et al.

Synaptic vesicle size and number are regulated by a clathrin adaptor protein required for endocytosis. _Neuron_ 21, 1465–1475 (1998). CAS  PubMed  Google Scholar  * Kasprowicz, J. et al.

Inactivation of clathrin heavy chain inhibits synaptic recycling but allows bulk membrane uptake. _J. Cell Biol._ 182, 1007–1016 (2008). CAS  PubMed  PubMed Central  Google Scholar  *

Heerssen, H., Fetter, R. D. & Davis, G. W. Clathrin dependence of synaptic-vesicle formation at the _Drosophila_ neuromuscular junction. _Curr. Biol._ 18, 401–409 (2008). CAS  PubMed 

PubMed Central  Google Scholar  * Koh, T. W., Verstreken, P. & Bellen, H. J. Dap160/intersectin acts as a stabilizing scaffold required for synaptic development and vesicle endocytosis.

_Neuron_ 43, 193–205 (2004). CAS  PubMed  Google Scholar  * Ramaswami, M., Rao, S., van der Bliek, A., Kelly, R. B. & Krishnan, K. S. Genetic studies on dynamin function in _Drosophila_.

_J. Neurogenet._ 9, 73–87 (1993). CAS  PubMed  Google Scholar  * Verstreken, P. et al. Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release. _Cell_ 109,

101–112 (2002). CAS  PubMed  Google Scholar  * Yao, C. K. et al. A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis. _Cell_ 138, 947–960

(2009). CAS  PubMed  PubMed Central  Google Scholar  * Phillips, A. M., Ramaswami, M. & Kelly, L. E. Stoned. _Traffic_ 11, 16–24. * Verstreken, P. et al. Synaptojanin is recruited by

endophilin to promote synaptic vesicle uncoating. _Neuron_ 40, 733–748 (2003). CAS  PubMed  Google Scholar  * Verstreken, P. et al. Tweek, an evolutionarily conserved protein, is required

for synaptic vesicle recycling. _Neuron_ 63, 203–215 (2009). CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We would like to thank B. Ganetzky, S.

Yamamoto, M. Rasband, N. Giagtzoglou, M. Xue, J. Kiger, H. Dierick, K. Cook, K. Schulze and B. Hassan for reading the manuscript. We apologize to all our colleagues whose work was not cited

because of space constraints. HJB is an investigator of the Howard Hughes Medical Institute, HT is supported by the Amyotrophic Lateral Sclerosis Association and CT is supported by a T32

from the National Institute of Neurological Disorders. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * and is at the Department of Neuroscience, Hugo J. Bellen is Director of the the Program

in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA., Hugo J. Bellen * Chao Tong and Hiroshi Tsuda are at the Department of Molecular and Human

Genetics, Hugo J. Bellen, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA., Hugo J. Bellen, Chao Tong & Hiroshi Tsuda * Hugo J. Bellen and Hiroshi Tsuda are at

the Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA., Hugo J. Bellen & Hiroshi Tsuda Authors * Hugo J. Bellen View author

publications You can also search for this author inPubMed Google Scholar * Chao Tong View author publications You can also search for this author inPubMed Google Scholar * Hiroshi Tsuda View

author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Hugo J. Bellen. ETHICS DECLARATIONS COMPETING INTERESTS The authors

declare no competing financial interests. RELATED LINKS RELATED LINKS DATABASES OMIM CADASIL familial advanced sleep phase syndrome hereditary motor and sensory neuropathy type IIC LQT

syndrome mucolipidosis type IV disease Parkinson's disease FURTHER INFORMATION Hugo J. Bellen's homepage RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE

THIS ARTICLE Bellen, H., Tong, C. & Tsuda, H. 100 years of _Drosophila_ research and its impact on vertebrate neuroscience: a history lesson for the future. _Nat Rev Neurosci_ 11,

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