Ascl1 Genetics Reveals Insights into Cerebellum Local Circuit Assembly

• DOI: 10.1523/jneurosci.0479-11.2011
• Publication Date: 2011-07-27T17:01:08Z
• Authors: A. Sudarov; R. K. Turnbull; E. J. Kim; M. Lebel-Potter; F. Guillemot; A. L. Joyner
• Keywords: Fate mapping

Two recently generated targeted mouse alleles of the neurogenic gene <i>Ascl1</i> were used to characterize cerebellum circuit formation. First, genetic inducible fate mapping (GIFM) with an <i>Ascl1^CreER</i> allele was found specifically mark all glial and neuron cell types that arise from ventricular zone (vz). Moreover, each type has a unique temporal profile marking GIFM. Of great utility, Purkinje cells (Pcs), early cohort Bergmann glia, four classes GABAergic interneurons can be genetically birth dated during embryogenesis using Astrocytes oligodendrocytes, in contrast, express throughout their proliferative phase white matter. Interestingly, final position acquires differs depending on when it expresses <i>Ascl1</i>. Interneurons (including candelabrum) attain more outside later they <i>Ascl1</i>, whereas Pcs have distinct settling patterns day Second, conditional allele, we discovered is differentially required for generation most vz-derived cells. Mice lacking major decrease three tendency toward loss later-born interneurons, as well imbalance oligodendrocytes astrocytes. Double-mutant analysis indicates related helix-loop-helix protein, Ptf1a, functions Ascl1 generating Pcs. By mutants, further plays specific role time period are restricting vz progenitors becoming rhombic lip progenitors.