Abstract
Neurons and glial cells depend on similar developmental pathways and often originate from common precursors; however, the differentiation of one or the other cell type depends on the activation of cell-specific pathways. In Drosophila, the differentiation of glial cells depends on a transcription factor, Glide/Gcm. This glial-promoting factor is both necessary and sufficient to induce the central and peripheral glial fates at the expense of the neuronal fate. In a screen for mutations affecting the adult peripheral nervous system, we have found a dominant mutation inducing supernumerary sensory organs. Surprisingly, this mutation is allelic to glide/gcm and induces precocious glide/gcm expression, which, in turn, activates the proneural genes. As a consequence, sensory organs are induced. Thus, temporal misregulation of the Glide/Gcm glial-promoting factor reveals a novel potential for this cell fate determinant. At the molecular level, this implies unpredicted features of the glide/gcm pathway. These findings also emphasize the requirement for both spatial and temporal glide/gcm regulation to achieve proper cell specification within the nervous system.
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Selected References
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- Akiyama Y., Hosoya T., Poole A. M., Hotta Y. The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14912–14916. doi: 10.1073/pnas.93.25.14912. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ambros V., Horvitz H. R. Heterochronic mutants of the nematode Caenorhabditis elegans. Science. 1984 Oct 26;226(4673):409–416. doi: 10.1126/science.6494891. [DOI] [PubMed] [Google Scholar]
- Artavanis-Tsakonas S., Rand M. D., Lake R. J. Notch signaling: cell fate control and signal integration in development. Science. 1999 Apr 30;284(5415):770–776. doi: 10.1126/science.284.5415.770. [DOI] [PubMed] [Google Scholar]
- Bernardoni R., Kammerer M., Vonesch J. L., Giangrande A. Gliogenesis depends on glide/gcm through asymmetric division of neuroglioblasts. Dev Biol. 1999 Dec 1;216(1):265–275. doi: 10.1006/dbio.1999.9511. [DOI] [PubMed] [Google Scholar]
- Bernardoni R., Miller A. A., Giangrande A. Glial differentiation does not require a neural ground state. Development. 1998 Aug;125(16):3189–3200. doi: 10.1242/dev.125.16.3189. [DOI] [PubMed] [Google Scholar]
- Bernardoni R., Vivancos V., Giangrande A. glide/gcm is expressed and required in the scavenger cell lineage. Dev Biol. 1997 Nov 1;191(1):118–130. doi: 10.1006/dbio.1997.8702. [DOI] [PubMed] [Google Scholar]
- Bossing T., Udolph G., Doe C. Q., Technau G. M. The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm. Dev Biol. 1996 Oct 10;179(1):41–64. doi: 10.1006/dbio.1996.0240. [DOI] [PubMed] [Google Scholar]
- Bryant P. J., Huettner B., Held L. I., Jr, Ryerse J., Szidonya J. Mutations at the fat locus interfere with cell proliferation control and epithelial morphogenesis in Drosophila. Dev Biol. 1988 Oct;129(2):541–554. doi: 10.1016/0012-1606(88)90399-5. [DOI] [PubMed] [Google Scholar]
- Campbell G., Göring H., Lin T., Spana E., Andersson S., Doe C. Q., Tomlinson A. RK2, a glial-specific homeodomain protein required for embryonic nerve cord condensation and viability in Drosophila. Development. 1994 Oct;120(10):2957–2966. doi: 10.1242/dev.120.10.2957. [DOI] [PubMed] [Google Scholar]
- Campuzano S., Carramolino L., Cabrera C. V., Ruíz-Gómez M., Villares R., Boronat A., Modolell J. Molecular genetics of the achaete-scute gene complex of D. melanogaster. Cell. 1985 Feb;40(2):327–338. doi: 10.1016/0092-8674(85)90147-3. [DOI] [PubMed] [Google Scholar]
- Campuzano S., Modolell J. Patterning of the Drosophila nervous system: the achaete-scute gene complex. Trends Genet. 1992 Jun;8(6):202–208. doi: 10.1016/0168-9525(92)90234-u. [DOI] [PubMed] [Google Scholar]
- Condron B. G., Zinn K. The grasshopper median neuroblast is a multipotent progenitor cell that generates glia and neurons in distinct temporal phases. J Neurosci. 1994 Oct;14(10):5766–5777. doi: 10.1523/JNEUROSCI.14-10-05766.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cubas P., de Celis J. F., Campuzano S., Modolell J. Proneural clusters of achaete-scute expression and the generation of sensory organs in the Drosophila imaginal wing disc. Genes Dev. 1991 Jun;5(6):996–1008. doi: 10.1101/gad.5.6.996. [DOI] [PubMed] [Google Scholar]
- Davis A. A., Temple S. A self-renewing multipotential stem cell in embryonic rat cerebral cortex. Nature. 1994 Nov 17;372(6503):263–266. doi: 10.1038/372263a0. [DOI] [PubMed] [Google Scholar]
- Diez del Corral R., Aroca P., G mez-Skarmeta J. L., Cavodeassi F., Modolell J. The Iroquois homeodomain proteins are required to specify body wall identity in Drosophila. Genes Dev. 1999 Jul 1;13(13):1754–1761. doi: 10.1101/gad.13.13.1754. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farkas G., Leibovitch B. A., Elgin S. C. Chromatin organization and transcriptional control of gene expression in Drosophila. Gene. 2000 Aug 8;253(2):117–136. doi: 10.1016/s0378-1119(00)00240-7. [DOI] [PubMed] [Google Scholar]
- García-Bellido A., Santamaria P. Developmental Analysis of the Achaete-Scute System of DROSOPHILA MELANOGASTER. Genetics. 1978 Mar;88(3):469–486. doi: 10.1093/genetics/88.3.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
- García-García M. J., Ramain P., Simpson P., Modolell J. Different contributions of pannier and wingless to the patterning of the dorsal mesothorax of Drosophila. Development. 1999 Aug;126(16):3523–3532. doi: 10.1242/dev.126.16.3523. [DOI] [PubMed] [Google Scholar]
- Garoia F., Guerra D., Pezzoli M. C., López-Varea A., Cavicchi S., García-Bellido A. Cell behaviour of Drosophila fat cadherin mutations in wing development. Mech Dev. 2000 Jun;94(1-2):95–109. doi: 10.1016/s0925-4773(00)00306-3. [DOI] [PubMed] [Google Scholar]
- Gho M., Bellaïche Y., Schweisguth F. Revisiting the Drosophila microchaete lineage: a novel intrinsically asymmetric cell division generates a glial cell. Development. 1999 Aug;126(16):3573–3584. doi: 10.1242/dev.126.16.3573. [DOI] [PubMed] [Google Scholar]
- Ghysen A., Dambly-Chaudiere C. Genesis of the Drosophila peripheral nervous system. Trends Genet. 1989 Aug;5(8):251–255. doi: 10.1016/0168-9525(89)90097-8. [DOI] [PubMed] [Google Scholar]
- Ghysen A., Dambly-Chaudière C., Jan L. Y., Jan Y. N. Cell interactions and gene interactions in peripheral neurogenesis. Genes Dev. 1993 May;7(5):723–733. doi: 10.1101/gad.7.5.723. [DOI] [PubMed] [Google Scholar]
- Giangrande A., Murray M. A., Palka J. Development and organization of glial cells in the peripheral nervous system of Drosophila melanogaster. Development. 1993 Mar;117(3):895–904. doi: 10.1242/dev.117.3.895. [DOI] [PubMed] [Google Scholar]
- Giangrande A. Proneural genes influence gliogenesis in Drosophila. Development. 1995 Feb;121(2):429–438. doi: 10.1242/dev.121.2.429. [DOI] [PubMed] [Google Scholar]
- Gomez-Skarmeta J. L., Diez del Corral R., de la Calle-Mustienes E., Ferré-Marcó D., Modolell J. Araucan and caupolican, two members of the novel iroquois complex, encode homeoproteins that control proneural and vein-forming genes. Cell. 1996 Apr 5;85(1):95–105. doi: 10.1016/s0092-8674(00)81085-5. [DOI] [PubMed] [Google Scholar]
- Grillenzoni N., van Helden J., Dambly-Chaudière C., Ghysen A. The iroquois complex controls the somatotopy of Drosophila notum mechanosensory projections. Development. 1998 Sep;125(18):3563–3569. doi: 10.1242/dev.125.18.3563. [DOI] [PubMed] [Google Scholar]
- Guillemot F. Vertebrate bHLH genes and the determination of neuronal fates. Exp Cell Res. 1999 Dec 15;253(2):357–364. doi: 10.1006/excr.1999.4717. [DOI] [PubMed] [Google Scholar]
- Gupta B. P., Rodrigues V. Atonal is a proneural gene for a subset of olfactory sense organs in Drosophila. Genes Cells. 1997 Mar;2(3):225–233. doi: 10.1046/j.1365-2443.1997.d01-312.x. [DOI] [PubMed] [Google Scholar]
- Gómez-Skarmeta J. L., Rodríguez I., Martínez C., Culí J., Ferrés-Marcó D., Beamonte D., Modolell J. Cis-regulation of achaete and scute: shared enhancer-like elements drive their coexpression in proneural clusters of the imaginal discs. Genes Dev. 1995 Aug 1;9(15):1869–1882. doi: 10.1101/gad.9.15.1869. [DOI] [PubMed] [Google Scholar]
- Halter D. A., Urban J., Rickert C., Ner S. S., Ito K., Travers A. A., Technau G. M. The homeobox gene repo is required for the differentiation and maintenance of glia function in the embryonic nervous system of Drosophila melanogaster. Development. 1995 Feb;121(2):317–332. doi: 10.1242/dev.121.2.317. [DOI] [PubMed] [Google Scholar]
- Hartenstein V., Posakony J. W. A dual function of the Notch gene in Drosophila sensillum development. Dev Biol. 1990 Nov;142(1):13–30. doi: 10.1016/0012-1606(90)90147-b. [DOI] [PubMed] [Google Scholar]
- Hartenstein V., Posakony J. W. Development of adult sensilla on the wing and notum of Drosophila melanogaster. Development. 1989 Oct;107(2):389–405. doi: 10.1242/dev.107.2.389. [DOI] [PubMed] [Google Scholar]
- Heinemeyer T., Chen X., Karas H., Kel A. E., Kel O. V., Liebich I., Meinhardt T., Reuter I., Schacherer F., Wingender E. Expanding the TRANSFAC database towards an expert system of regulatory molecular mechanisms. Nucleic Acids Res. 1999 Jan 1;27(1):318–322. doi: 10.1093/nar/27.1.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heitzler P., Haenlin M., Ramain P., Calleja M., Simpson P. A genetic analysis of pannier, a gene necessary for viability of dorsal tissues and bristle positioning in Drosophila. Genetics. 1996 Jul;143(3):1271–1286. doi: 10.1093/genetics/143.3.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hinz U., Giebel B., Campos-Ortega J. A. The basic-helix-loop-helix domain of Drosophila lethal of scute protein is sufficient for proneural function and activates neurogenic genes. Cell. 1994 Jan 14;76(1):77–87. doi: 10.1016/0092-8674(94)90174-0. [DOI] [PubMed] [Google Scholar]
- Hosoya T., Takizawa K., Nitta K., Hotta Y. glial cells missing: a binary switch between neuronal and glial determination in Drosophila. Cell. 1995 Sep 22;82(6):1025–1036. doi: 10.1016/0092-8674(95)90281-3. [DOI] [PubMed] [Google Scholar]
- Huang F., Dambly-Chaudière C., Ghysen A. The emergence of sense organs in the wing disc of Drosophila. Development. 1991 Apr;111(4):1087–1095. doi: 10.1242/dev.111.4.1087. [DOI] [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. 1993 Jul 2;73(7):1307–1321. doi: 10.1016/0092-8674(93)90358-w. [DOI] [PubMed] [Google Scholar]
- Jones B. W., Fetter R. D., Tear G., Goodman C. S. glial cells missing: a genetic switch that controls glial versus neuronal fate. Cell. 1995 Sep 22;82(6):1013–1023. doi: 10.1016/0092-8674(95)90280-5. [DOI] [PubMed] [Google Scholar]
- Kageyama R., Ishibashi M., Takebayashi K., Tomita K. bHLH transcription factors and mammalian neuronal differentiation. Int J Biochem Cell Biol. 1997 Dec;29(12):1389–1399. doi: 10.1016/s1357-2725(97)89968-2. [DOI] [PubMed] [Google Scholar]
- Kammerer M., Giangrande A. Glide2, a second glial promoting factor in Drosophila melanogaster. EMBO J. 2001 Sep 3;20(17):4664–4673. doi: 10.1093/emboj/20.17.4664. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leber S. M., Breedlove S. M., Sanes J. R. Lineage, arrangement, and death of clonally related motoneurons in chick spinal cord. J Neurosci. 1990 Jul;10(7):2451–2462. doi: 10.1523/JNEUROSCI.10-07-02451.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller A. A., Bernardoni R., Giangrande A. Positive autoregulation of the glial promoting factor glide/gcm. EMBO J. 1998 Nov 2;17(21):6316–6326. doi: 10.1093/emboj/17.21.6316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller A. A., Bernardoni R., Hindelang C., Kammerer M., Sorrentino S., Van de Bor V., Giangrande A. Role and mechanism of action of glial cell deficient/glial cell missing (glide/gcm), the fly glial promoting factor. Adv Exp Med Biol. 1999;468:33–46. doi: 10.1007/978-1-4615-4685-6_4. [DOI] [PubMed] [Google Scholar]
- Miller A. A., Bernardoni R., Hindelang C., Kammerer M., Sorrentino S., Van de Bor V., Giangrande A. Role and mechanism of action of glial cell deficient/glial cell missing (glide/gcm), the fly glial promoting factor. Adv Exp Med Biol. 1999;468:33–46. doi: 10.1007/978-1-4615-4685-6_4. [DOI] [PubMed] [Google Scholar]
- Orgogozo V., Schweisguth F., Bellaïche Y. Lineage, cell polarity and inscuteable function in the peripheral nervous system of the Drosophila embryo. Development. 2001 Mar;128(5):631–643. doi: 10.1242/dev.128.5.631. [DOI] [PubMed] [Google Scholar]
- Parks A. L., Muskavitch M. A. Delta function is required for bristle organ determination and morphogenesis in Drosophila. Dev Biol. 1993 Jun;157(2):484–496. doi: 10.1006/dbio.1993.1151. [DOI] [PubMed] [Google Scholar]
- Ragone G., Bernardoni R., Giangrande A. A novel mode of asymmetric division identifies the fly neuroglioblast 6-4T. Dev Biol. 2001 Jul 1;235(1):74–85. doi: 10.1006/dbio.2001.0296. [DOI] [PubMed] [Google Scholar]
- Ramain P., Heitzler P., Haenlin M., Simpson P. pannier, a negative regulator of achaete and scute in Drosophila, encodes a zinc finger protein with homology to the vertebrate transcription factor GATA-1. Development. 1993 Dec;119(4):1277–1291. doi: 10.1242/dev.119.4.1277. [DOI] [PubMed] [Google Scholar]
- Reddy G. V., Gupta B., Ray K., Rodrigues V. Development of the Drosophila olfactory sense organs utilizes cell-cell interactions as well as lineage. Development. 1997 Feb;124(3):703–712. doi: 10.1242/dev.124.3.703. [DOI] [PubMed] [Google Scholar]
- Reddy G. V., Rodrigues V. A glial cell arises from an additional division within the mechanosensory lineage during development of the microchaete on the Drosophila notum. Development. 1999 Oct;126(20):4617–4622. doi: 10.1242/dev.126.20.4617. [DOI] [PubMed] [Google Scholar]
- Reinhart B. J., Ruvkun G. Isoform-specific mutations in the Caenorhabditis elegans heterochronic gene lin-14 affect stage-specific patterning. Genetics. 2001 Jan;157(1):199–209. doi: 10.1093/genetics/157.1.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Romani S., Campuzano S., Macagno E. R., Modolell J. Expression of achaete and scute genes in Drosophila imaginal discs and their function in sensory organ development. Genes Dev. 1989 Jul;3(7):997–1007. doi: 10.1101/gad.3.7.997. [DOI] [PubMed] [Google Scholar]
- Ruiz-Gómez M., Modolell J. Deletion analysis of the achaete-scute locus of Drosophila melanogaster. Genes Dev. 1987 Dec;1(10):1238–1246. doi: 10.1101/gad.1.10.1238. [DOI] [PubMed] [Google Scholar]
- Schmid A., Chiba A., Doe C. Q. Clonal analysis of Drosophila embryonic neuroblasts: neural cell types, axon projections and muscle targets. Development. 1999 Nov;126(21):4653–4689. doi: 10.1242/dev.126.21.4653. [DOI] [PubMed] [Google Scholar]
- Schmidt H., Rickert C., Bossing T., Vef O., Urban J., Technau G. M. The embryonic central nervous system lineages of Drosophila melanogaster. II. Neuroblast lineages derived from the dorsal part of the neuroectoderm. Dev Biol. 1997 Sep 15;189(2):186–204. doi: 10.1006/dbio.1997.8660. [DOI] [PubMed] [Google Scholar]
- Schreiber J., Sock E., Wegner M. The regulator of early gliogenesis glial cells missing is a transcription factor with a novel type of DNA-binding domain. Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4739–4744. doi: 10.1073/pnas.94.9.4739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van De Bor V., Walther R., Giangrande A. Some fly sensory organs are gliogenic and require glide/gcm in a precursor that divides symmetrically and produces glial cells. Development. 2000 Sep;127(17):3735–3743. doi: 10.1242/dev.127.17.3735. [DOI] [PubMed] [Google Scholar]
- Vincent S., Vonesch J. L., Giangrande A. Glide directs glial fate commitment and cell fate switch between neurones and glia. Development. 1996 Jan;122(1):131–139. doi: 10.1242/dev.122.1.131. [DOI] [PubMed] [Google Scholar]
- Williams B. P., Read J., Price J. The generation of neurons and oligodendrocytes from a common precursor cell. Neuron. 1991 Oct;7(4):685–693. doi: 10.1016/0896-6273(91)90381-9. [DOI] [PubMed] [Google Scholar]
- Xiong W. C., Okano H., Patel N. H., Blendy J. A., Montell C. repo encodes a glial-specific homeo domain protein required in the Drosophila nervous system. Genes Dev. 1994 Apr 15;8(8):981–994. doi: 10.1101/gad.8.8.981. [DOI] [PubMed] [Google Scholar]
- Zecca M., Basler K., Struhl G. Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing. Development. 1995 Aug;121(8):2265–2278. doi: 10.1242/dev.121.8.2265. [DOI] [PubMed] [Google Scholar]
