The goal of Project 5 is to analyze the molecular mechanisms which result in cell type and developmental stage specific expression of novel genes that are tightly regulated during cerebellar granule cell differentiation, with particular emphasis on those genes which require specific cell-cell interactions as signals for normal expression. Toward this goal, we will (1) Complete the characterization of a collection of cerebellar cDNAs which we have recently cloned from a stage specific granule cell cDNA library, screening for developmental stage and tissue specific expression. (2) Define the temporal and spatial patterns of expression of regulated clones by in situ hybridization of tissue from normal and neurologic mutant mice (including Lurcher (Lc), weaver (wv), and nervous (nr)) and (3) Isolate both full-length cDNAs and genomic clones of select tightly regulated novel cDNAs as tools for further analysis. To examine the transcriptional regulation of granule cell specific genes, we will carry out transient expression assays in cerebellar slice preparations and analyze critical constructs in transgenic mice. The transcription factors which interact with granule cell specific genes will be examined with particular emphasis on signal transduction pathways mediated by specific cell-cell interactions. Finally, we will examine the functions of selected gene products by (1) in-depth computer analysis of cDNA sequences, (2) immunocytochemical localization of polyclonal antisera against expressed gene products, (3) functional perturbation studies in vitro (see Project 4), and (4) molecular genetic perturbation studies in vivo.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Type
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Plump, Andrew S; Erskine, Lynda; Sabatier, Christelle et al. (2002) Slit1 and Slit2 cooperate to prevent premature midline crossing of retinal axons in the mouse visual system. Neuron 33:219-32
Ibanez-Tallon, Ines; Gorokhova, Svetlana; Heintz, Nathaniel (2002) Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus. Hum Mol Genet 11:715-21
Ibanez-Tallon, Ines; Miwa, Julie M; Wang, Hai Long et al. (2002) Novel modulation of neuronal nicotinic acetylcholine receptors by association with the endogenous prototoxin lynx1. Neuron 33:893-903
Espinosa, F; McMahon, A; Chan, E et al. (2001) Alcohol hypersensitivity, increased locomotion, and spontaneous myoclonus in mice lacking the potassium channels Kv3.1 and Kv3.3. J Neurosci 21:6657-65
Bhatt, R S; Tomoda, T; Fang, Y et al. (2000) Discoidin domain receptor 1 functions in axon extension of cerebellar granule neurons. Genes Dev 14:2216-28
Heintz, N (2000) Analysis of mammalian central nervous system gene expression and function using bacterial artificial chromosome-mediated transgenesis. Hum Mol Genet 9:937-43
Doughty, M L; De Jager, P L; Korsmeyer, S J et al. (2000) Neurodegeneration in Lurcher mice occurs via multiple cell death pathways. J Neurosci 20:3687-94
Mason, C; Erskine, L (2000) Growth cone form, behavior, and interactions in vivo: retinal axon pathfinding as a model. J Neurobiol 44:260-70
Erskine, L; Williams, S E; Brose, K et al. (2000) Retinal ganglion cell axon guidance in the mouse optic chiasm: expression and function of robos and slits. J Neurosci 20:4975-82
Tomoda, T; Bhatt, R S; Kuroyanagi, H et al. (1999) A mouse serine/threonine kinase homologous to C. elegans UNC51 functions in parallel fiber formation of cerebellar granule neurons. Neuron 24:833-46

Showing the most recent 10 out of 37 publications