The progenitors in the ventral mesencephalon mutually regulate the induction and cessation of Shh and Gli1 expression for proper dopamine neuron specification

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NICHD	DEV-4

Authors

• L Hayes
• M Zervas
• S Ahn

Abstract

Sonic hedgehog (Shh) signaling is important for proper patterning and cell fate specification of diverse tissues. Using genetic inducible fate mapping (GIFM) we found that timing of Shh and Gli1 (Shh-responsiveness) expression within the ventral mesencephalon (vMes) segregates midbrain dopamine (mDA) neuron progenitors into spatial subdomains that generate the mDA neurons of the ventral tegmental area and substantia nigra pars compacta. Interestingly, the cumulative lineage contribution of both Shh and Gli1 was largely overlapping in mDA neurons despite their distinct temporal expression patterns within the vMes. By comparing the short-term lineage and current expression of Gli1 and Shh in vMes progenitors, we demonstrate that the same cells express Gli1 and Shh with a temporal delay, providing the basis for similar cumulative lineage contributions. In addition, we determined the requirement of Shh-responsiveness for later Shh induction and the role of down-regulation of Shh signaling in maintenance of Shh expression and specification of vMes progenitors. Together, our study on the relationship between the Shh-secreting and –responding cells reveals an intricate regulation of induction and cessation of Shh signaling in the vMes for proper specification and development of mDA neurons.

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