Abstract
Generation of distinct ventral neuronal
subtypes in the developing spinal cord requires Shh signaling mediated
by the Gli family of transcription factors. Genetic studies of Shh−/−;Gli3−/−
double mutants indicated that the inhibition of Gli3 repressor activity
by Shh is sufficient for the generation of different neurons including
motor neurons. In this study, we show that although ventral neural
progenitors are initiated in normal numbers in Shh−/−;Gli3−/− mutants, the subsequent appearance of motor neuron progenitors shows a 
20-hour
lag, concomitant with a delay in the activation of a pan-neuronal
differentiation program and cell cycle exit of ventral neural
progenitors. Accordingly, the Shh−/−;Gli3−/−
mutant spinal cord exhibits a delay in motor neuron differentiation and
an accumulation of a ventral neural progenitor pool. The requirement of
Shh and Gli3 activities to promote the timely appearance of motor
neuron progenitors is further supported by the analysis of Ptch1−/−
mutants, in which constitutive Shh pathway activity is sufficient to
elicit ectopic and premature differentiation of motor neurons at the
expense of ventral neural progenitors. Taken together, our analysis
suggests that, beyond its well established dorso-ventral patterning
function through a Gli3-derepression mechanism, Shh signaling is
additionally required to promote the timely appearance of motor neuron
progenitors in the developing spinal cord.