INTERACTIONS--SIGNALING PATHWAYS--NEURONAL SPECIFICATION

$0P01FY2002HDNIH

University Of Oregon, Eugene OR

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Abstract

Patterning the central nervous system is a key feature of embryogenesis. Several signaling systems are essential in patterning the hindbrain and spinal cord., including secreted signals such as fibroblast growth factors (Fgfs), neurotrophins, and ligands of such as retinoic acid (RA), and local signals such as Delta/Notch. While these signaling mechanisms have been extensively studied individually, there has been little work investigating how different signaling mechanisms act coordinately during nervous system patterning. Aim 2 is to determine whether RA regulates the number and pattern of Rohon-Beard (RB) sensory neurons by suppressing Delta/Notch signaling. Aim 3 seeks to uncover mutations that disrupt pattern formation and cell fates in the hindbrain and in the RB neurons by phenotype-driven screens and by screens for mutations in cloned genes. Achieving these aims will help us to understand development of the hindbrain, which has been implicated in human diseases such as autism and L-DOPA unresponsive parkinsonism, and development of sensory neurons, responsible for perception of pain and other sensory modalities.

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