Temporal regulation by Sonic Hedgehog of neural pr.. (TempIntShh)
Temporal regulation by Sonic Hedgehog of neural progenitor identity during vertebrate neurogenesis
Start date: 12 Aug 2008,
End date: 11 Aug 2010
The central nervous system (CNS) is the most complex organ in the vertebrate body, and the patterning of the developing CNS is comprised of a large number of regulatory steps. Many extracellular molecules play critical roles in the precise patterning of the CNS during embryonic development. Among them, Sonic Hedgehog (Shh), a soluble factor produced by the floor plate and notochord, is a strong candidate for the determination of the cell fates in the ventral neural tube. Shh has the characteristics of a “morphogen”- it functions at long range in a concentration dependent fashion to induce several different cell types. How Shh is perceived and interpreted by the receiving cells and consequently gives rise to diversity of cell fates has long been a central problem in neural development. In a recent study, the host laboratory have found that transcription factors of the Gli family are the intracellular mediators that transduce the concentration dependent aspect of Shh signaling; the data suggest that the transcriptional activity of Gli proteins are proportional to the concentration of Shh. However, the duration of Shh signaling also appears to contribute to the inducing activity of Shh. However how cells perceive and integrate the duration of Shh signaling as well as the concentration remains to be determined. To address this issue, this project will define the competence period of the neural progenitors for the Shh signaling and analyse how the temporal regulation of Shh signaling in the development of the ventral neural tube influences cell fate. To this end, we will take advantage of a combination of methodologies that use chick electroporation, time-dependent knock-out mice and zebrafish systems. The aim is to understand the mechanisms by which the competence of undifferentiated pluripotent neural cells to inductive cues is regulated and how progenitors acquire their distinct differentiated characteristics in response to the morphogen activity of Shh signaling.
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