Abstract

The mammalian central nervous system (CNS) contains a most diverse group of neurons. How are neuronal cell fate specified during development? Relatively little is known about the molecular mechanisms utilized in generating cell diversity in the vertebrate CNS. Our approach to this problem is to make use of the wealth of information gathered from the study of neuronal cell fate specification in the fruit fly Drosophila by identifying mammalian homologs of genes which are important in fly neural development. By using our Drosophila development work as a guide, we believe that we have identified genes which are likely to play key roles in three important but relatively unexplored area of vertebrate neural development, namely neuronal cell fate specification, asymmetric cell division and initiation of axon outgrowth. Our major focus in the next few years will be the experimental tests of the following hypothesis; (1) vertebrate atonal controls the initiation of the retinal neuronal development, (2) mouse numb controls asymmetric cell division and cell lineage in mouse neurogenesis,, (3) mouse rac/cdc42 controls the neuronal morphogenesis, especially axon outgrowth and dendritic spine formation, (4) some of those genes are also involved in long term synaptic plasticity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH048200-10
Application #
6346243
Study Section
Project Start
2000-09-01
Project End
2002-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
10
Fiscal Year
2000
Total Cost
$175,747
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Paredes, Alfonso; Romero, Carmen; Dissen, Gregory A et al. (2004) TrkB receptors are required for follicular growth and oocyte survival in the mammalian ovary. Dev Biol 267:430-49
Rohrer, B; Matthes, M T; LaVail, M M et al. (2003) Lack of p75 receptor does not protect photoreceptors from light-induced cell death. Exp Eye Res 76:125-9
Jullien, Jerome; Guili, Vincent; Reichardt, Louis F et al. (2002) Molecular kinetics of nerve growth factor receptor trafficking and activation. J Biol Chem 277:38700-8
Farinas, I; Jones, K R; Tessarollo, L et al. (2001) Spatial shaping of cochlear innervation by temporally regulated neurotrophin expression. J Neurosci 21:6170-80
Mischel, P S; Smith, S G; Vining, E R et al. (2001) The extracellular domain of p75NTR is necessary to inhibit neurotrophin-3 signaling through TrkA. J Biol Chem 276:11294-301
Xu, B; Gottschalk, W; Chow, A et al. (2000) The role of brain-derived neurotrophic factor receptors in the mature hippocampus: modulation of long-term potentiation through a presynaptic mechanism involving TrkB. J Neurosci 20:6888-97
Rohrer, B; Korenbrot, J I; LaVail, M M et al. (1999) Role of neurotrophin receptor TrkB in the maturation of rod photoreceptors and establishment of synaptic transmission to the inner retina. J Neurosci 19:8919-30
Huang, E J; Wilkinson, G A; Farinas, I et al. (1999) Expression of Trk receptors in the developing mouse trigeminal ganglion: in vivo evidence for NT-3 activation of TrkA and TrkB in addition to TrkC. Development 126:2191-203
Mistretta, C M; Goosens, K A; Farinas, I et al. (1999) Alterations in size, number, and morphology of gustatory papillae and taste buds in BDNF null mutant mice demonstrate neural dependence of developing taste organs. J Comp Neurol 409:13-24
Francis, N; Farinas, I; Brennan, C et al. (1999) NT-3, like NGF, is required for survival of sympathetic neurons, but not their precursors. Dev Biol 210:411-27

Showing the most recent 10 out of 31 publications