Abstract

The overall goal of this project is to provide information on the mechanisms that control the specification of granule cell fate in the cerebellar cortex. In the proposed research, we will examine, at the cellular and molecular levels, the signals that control the differentiation of precursor cells derived from the external germinal layer (EGL) of the mouse cerebellar cortex, using an in vitro model system developed in our laboratory. Two issues will be addressed. First, we will determine whether growth factors, in particular those with high levels of expression in developing cerebellum (bFGF, NT3 and BDNF) regulate granule cell specification. Second, to provide a genetic analysis of granule cell determination, we will analyze EGL precursor cells from the neurological mutant mouse weaver, an animal with phenotypic defects in granule cell differentiation, including a failure of neurite outgrowth and glial-guided migration.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS030532-05
Application #
5215375
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

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
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
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

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