Role of DE-cadherin in neuroblast proliferation, neural morphogenesis, and axon tract formation in Drosophila larval brain development.
In the wild-type brain, the Drosophila classic cadherin DE-cadherin is expressed globally by postembryonic neuroblasts and their lineages ("secondary lineages"), as well as glial cells. To address the role of DE-cadherin in the larval brain, we took advantage of the dominant-negative DE-cad(ex) construct, the expression of which was directed to neurons, glial cells, or both. Global expression of DE-cad(ex) driven by a heat pulse during the early second instar resulted in a severe phenotype that included deficits in neural proliferation. Neuroblasts appeared in approximately normal numbers but had highly reduced mitotic activity. When the DE-cad(ex) construct was driven by the glial-specific driver gcm-Gal4, the effect of DE-cad(ex) on neuroblast proliferation could be replicated, which indicates that DE-cadherin acts in glial cells to promote proliferation of neuroblasts. Expression of DE-cad(ex) in neurons, cortex glia, or both results in abnormalities in cortex layering and in trajectories of secondary axons. In the wild-type brain, neuroblasts and neurons generated at different time points are arranged concentrically around the neuropile, with the DE-cadherin-positive neuroblasts and young secondary neurons at the surface, followed by older secondary neurons and primary neurons. Axons of secondary lineages follow a straight radial course toward the neuropile. Processes of glial cells located in the cortex form a scaffold, called trophospongium, that enwraps neuroblasts and neurons. Expression of DE-cad(ex) in neurons, cortex glia, or both disrupted the regular placement of neuroblasts and secondary neurons and resulted in abnormal trajectories of cell body fiber tracts. We conclude that DE-cadherin plays a pivotal role in larval brain proliferation, brain cortex morphogenesis, and axon growth.
Dumstrei
Karin
K
Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA.
Wang
Fay
F
Hartenstein
Volker
V
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D019070:Cell Lineage; D002999:Clone Cells; D004330:Drosophila; D005799:Genes, Dominant; D007814:Larva; D009024:Morphogenesis / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D015820:Cadherins; D015815:Cell Adhesion Molecules