Distinct activities of MSX 1&3 in the spinal cord

Distinct activities of MSX 1&3 in the spinal cord -...

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Unformatted text preview: 1017 Introduction During the development of the vertebrate nervous system, multiple signaling pathways play instructive roles in patterning the dorsoventral axis of the neural tube. Sonic hedgehog secreted from the notochord and floor plate induces the differentiation of motoneurons and ventral interneurons in a concentration-dependent manner in the ventral neural tube (reviewed by Briscoe and Ericson, 2001). Similarly, signaling molecules secreted from the epidermal ectoderm and roof plate are involved in patterning the dorsal neural tube. Both Wnt and Bmp signaling pathways have been implicated to be important for dorsal neural tube patterning (Garcia-Castro et al., 2002; Liem et al., 1995; Nguyen et al., 2000). The downstream effectors that mediate these activities of Wnt and Bmp signaling in regulating dorsal neural tube development have been poorly defined. We address the roles of the Msx family of transcription factors in mediating downstream effects of Bmp signaling in chick neural tube development. Three populations of cells develop from the dorsal neural tube/lateral neural plate. Neural crest cells that give rise to the peripheral nervous system are generated from the border region between the neural plate and adjacent ectoderm and migrate out of the neural tube before or during neural tube closure (Le Douarin, 1982). Roof-plate cells develop at the dorsal midline of the neural tube and are a group of specialized glial cells. Both neural crest and roof-plate cells are induced by Bmp signals from the epidermal ectoderm (Liem et al., 1995). The roof-plate cells themselves subsequently become a source of several Bmps, which can promote the differentiation of a third population of cells, the dorsal spinal cord interneurons (Lee et al., 2000; Lee et al., 1998; Liem et al., 1997). Genetic studies of zebrafish mutants with different components of Bmp signaling pathways disrupted ( swirl/bmp2b , snailhouse/bmp7 and somitabun/smad5 ) provide direct evidence for the involvement of Bmps in the specification of neural crest and dorsal neurons (Barth et al., 1999; Nguyen et al., 2000). It is not clear how Bmp signaling can mediate such a diverse array of activities in the dorsal neural tube. It has been suggested that the competence of neural progenitor cells in the lateral neural plate/dorsal neural tube changes so that early progenitor cells generate neural crest and roof-plate cells in response to Bmp signaling whereas late progenitor cells generate dorsal interneurons, and in vitro explant studies provide evidence consistent with this hypothesis (Liem et al., 1997). Nevertheless, the question remains of what downstream effectors mediate these activities of Bmps, and whether different downstream mediators display a different subset of Bmp initiated activities. One group of candidate effectors for Bmp signaling is the Msx family of transcription factors....
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This note was uploaded on 09/29/2010 for the course BIOLOGY BISP 194 taught by Professor Hermann during the Fall '10 term at UCSD.

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Distinct activities of MSX 1&3 in the spinal cord -...

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