We are studying the molecular mechanisms controlling the segregation (delamination) of neuronal precursors in Drosophila. In order to move out of the neurectodermal epithelium, neuronal precursors undergo active changes of their cytoskeleton and contacts to neighboring cells. Since, according to recent findings, many of the genes controlling these processes are involved in the delamination of other (non-neural) tissues as well, our studies have a bearing on morphogenetic movements in general. These studies ultimately are also of clinical importance, because the molecules controlling cell movements during normal development (e.g., cadherins; homologs of Drosophila Notch and wingless genes) also play a central role in neoplastic growth. The specific objectives of this proposal are the molecular analysis of two genes involved in neuronal precursor segregation, faint sausage (fas) and shotgun (shg). Mutations in fas cause cytoskeletal changes in many epithelial cells, associated with the loss of polarity and monolayered arrangement of these cells. In the neurectoderm, these changes lead to defects in neuronal precursor delamination. In shg mutant embryos, there is a widespread degeneration of the neurectoderm (as well of other specialized epithelia). In the foregoing granting period, both fas and shg were characterized phenotypically and genetically. We have cloned fas with the help of a P1 plasmid crossing the fas breakpoint and a PlacZ insertion in fas. Cloning of shg was initiated by starting a walk in a cosmid library from a P1 plasmid. In this application experiments are proposed to identify the fas and shg transcripts and characterize their sequence and expression pattern. For both fas and shg, fusion proteins expressed in E. coli will be used to generate antibodies. Germline transformation of our isolated genomic clones will be attempted to rescue the mutations. We will screen for additional mutations affecting early neurogenesis. Work of the foregoing granting period had established that there exist similarities between cytoskeletal changes in delamination and mitosis, and that the pattern of these two processes in the neurectoderm are closely correlated. We have shown that two genes known to control elamination, Notch and wingless, have an effect on mitosis of neurectodermal cells as well. We here propose a set of developmental- genetic experiments which address the relationship between delamination and mitosis, and their control by neurogenic and segment polarity genes, in greater detail.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS029367-06
Application #
2037429
Study Section
Neurology C Study Section (NEUC)
Project Start
1991-05-01
Project End
1998-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Fung, Siaumin; Wang, Fay; Spindler, Shana R et al. (2009) Drosophila E-cadherin and its binding partner Armadillo/ beta-catenin are required for axonal pathway choices in the developing larval brain. Dev Biol 332:371-82
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Wang, Fay; Hartenstein, Volker (2006) Regulation of cell adhesion in the Drosophila embryo by phosphorylation of the cadherin-catenin-complex. Cell Tissue Res 324:157-66
Cardona, Albert; Hartenstein, Volker; Romero, Rafael (2006) Early embryogenesis of planaria: a cryptic larva feeding on maternal resources. Dev Genes Evol 216:667-81
de Velasco, Begona; Mandal, Lolitika; Mkrtchyan, Marianna et al. (2006) Subdivision and developmental fate of the head mesoderm in Drosophila melanogaster. Dev Genes Evol 216:39-51
Pereanu, Wayne; Hartenstein, Volker (2006) Neural lineages of the Drosophila brain: a three-dimensional digital atlas of the pattern of lineage location and projection at the late larval stage. J Neurosci 26:5534-53
Younossi-Hartenstein, Amelia; Nguyen, Bidong; Shy, Diana et al. (2006) Embryonic origin of the Drosophila brain neuropile. J Comp Neurol 497:981-98
Pereanu, Wayne; Shy, Diana; Hartenstein, Volker (2005) Morphogenesis and proliferation of the larval brain glia in Drosophila. Dev Biol 283:191-203

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