The differentiation of the nervous system depends on a sequence of related developmental decisions. These decisions - mediated by cell-cell interactions - include (1) the choice between neural versus non-neural cellular lineages, (2) the subsequent choice among the wide variety of specific neural cell fates, and (3) the choice of appropriate target cells with which to synapse. The long-term goal of this project is to understand the molecular basis of each of these important developmental decisions. In Project 1, led by Chris Kintner, we will study the role of a pair of interacting receptor-ligand proteins (Notch and Delta) in neural specification in the developing Xenopus embryo. In functional studies, we will test the hypothesis that, as in Drosophila, these two molecules play a determinative role in the initial choice of neural versus non- neural cell fate. In Project 2, led by Greg Lemke, we will study the structure and function of four new neural receptor tyrosines kinases (Tyrol 2, 3, and 6). Proteins related to the Tyros are known to function as receptors for neurotrophic regulators such as Nerve Growth Factor, and to directly control the choice between specific neural cell fates. In project 3, led by John Thomas, we have capitalized on the genetics of Drosophila to identify a gene (bendless) that controls the final choice of synaptic targets in a well-defined neuronal circuit. We will identify the bendless gene product and study its role in the target recognition process. These experiments will provide us with fundamental insights into the cellular interactions that mediate neural development, and a detailed understanding of their molecular basis.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
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Neurological Disorders Program Project Review B Committee (NSPB)
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Small, Judy A
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Salk Institute for Biological Studies
La Jolla
United States
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Zhang, Jingming; Lanuza, Guillermo M; Britz, Olivier et al. (2014) V1 and v2b interneurons secure the alternating flexor-extensor motor activity mice require for limbed locomotion. Neuron 82:138-50
Borowska, Joanna; Jones, Christopher T; Zhang, Han et al. (2013) Functional subpopulations of V3 interneurons in the mature mouse spinal cord. J Neurosci 33:18553-65
Levine, Ariel J; Lewallen, Kathryn A; Pfaff, Samuel L (2012) Spatial organization of cortical and spinal neurons controlling motor behavior. Curr Opin Neurobiol 22:812-21
Bonanomi, Dario; Chivatakarn, Onanong; Bai, Ge et al. (2012) Ret is a multifunctional coreceptor that integrates diffusible- and contact-axon guidance signals. Cell 148:568-82
Wang, Biao; Moya, Noel; Niessen, Sherry et al. (2011) A hormone-dependent module regulating energy balance. Cell 145:596-606
Bevins, Nicholas; Lemke, Greg; Reber, Michael (2011) Genetic dissection of EphA receptor signaling dynamics during retinotopic mapping. J Neurosci 31:10302-10
Alaynick, William A; Jessell, Thomas M; Pfaff, Samuel L (2011) SnapShot: spinal cord development. Cell 146:178-178.e1
Bai, Ge; Chivatakarn, Onanong; Bonanomi, Dario et al. (2011) Presenilin-dependent receptor processing is required for axon guidance. Cell 144:106-18
Grossmann, Katja S; Giraudin, Aurore; Britz, Olivier et al. (2010) Genetic dissection of rhythmic motor networks in mice. Prog Brain Res 187:19-37
Garcia-Campmany, Lidia; Stam, Floor J; Goulding, Martyn (2010) From circuits to behaviour: motor networks in vertebrates. Curr Opin Neurobiol 20:116-25

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