A mosaic genetic screen for genes necessary forDrosophilamushroom body neuronal morphogenesis
- 15 March 2003
- journal article
- Published by The Company of Biologists in Development
- Vol. 130 (6), 1203-1213
- https://doi.org/10.1242/dev.00319
Abstract
Neurons undergo extensive morphogenesis during development. To systematically identify genes important for different aspects of neuronal morphogenesis, we performed a genetic screen using the MARCM system in the mushroom body (MB) neurons of the Drosophila brain. Mutations on the right arm of chromosome 2 (which contains ∼20% of the Drosophila genome) were made homozygous in a small subset of uniquely labeled MB neurons. Independently mutagenized chromosomes (4600) were screened, yielding defects in neuroblast proliferation, cell size, membrane trafficking, and axon and dendrite morphogenesis. We report mutations that affect these different aspects of morphogenesis and phenotypically characterize a subset. We found that roadblock, which encodes a dynein light chain, exhibits reduced cell number in neuroblast clones, reduced dendritic complexity and defective axonal transport. These phenotypes are nearly identical to mutations in dynein heavy chain Dhc64 and in Lis1, the Drosophila homolog of human lissencephaly 1, reinforcing the role of the dynein complex in cell proliferation, dendritic morphogenesis and axonal transport. Phenotypic analysis of short stop/kakapo, which encodes a large cytoskeletal linker protein, reveals a novel function in regulating microtubule polarity in neurons. MB neurons mutant for flamingo, which encodes a seven transmembrane cadherin, extend processes beyond their wild-type dendritic territories. Overexpression of Flamingo results in axon retraction. Our results suggest that most genes involved in neuronal morphogenesis play multiple roles in different aspects of neural development, rather than performing a dedicated function limited to a specific process.Keywords
This publication has 42 references indexed in Scilit:
- Rac GTPases control axon growth, guidance and branchingNature, 2002
- A genetic analysis of the cytological region 46C-F containing the Drosophila melanogaster homolog of the jun proto-oncogeneMolecular Genetics and Genomics, 2001
- Regulating Axon Branch StabilityCell, 2001
- Control of Dendritic Field Formation in Drosophila: The Roles of Flamingo and Competition between Homologous NeuronsNeuron, 2000
- Microtubule-Based Transport Systems in Neurons: The Roles of Kinesins and DyneinsAnnual Review of Neuroscience, 2000
- Drosophila roadblock and Chlamydomonas LC7: A Conserved Family of Dynein-associated Proteins Involved in Axonal Transport, Flagellar Motility, and MitosisThe Journal of cell biology, 1999
- Microtubules and Neuronal Polarity: Lessons from MitosisNeuron, 1999
- Neuroanatomy: Mushrooming mushroom bodiesCurrent Biology, 1996
- Neuronal PolarityAnnual Review of Neuroscience, 1994
- Proliferation pattern of postembryonic neuroblasts in the brain of Drosophila melanogasterDevelopmental Biology, 1992