Niraj Trivedi

Abstract Evidence is lacking as to how developing neurons integrate mitogenic signals with microenvironment cues to control proliferation and differentiation. We determine that the Siah2 E3 ubiquitin ligase functions in a coincidence detection circuit linking responses to the Shh mitogen and the extracellular matrix to control cerebellar granule neurons (CGN) GZ occupancy. We show that Shh signaling maintains Siah2 expression in CGN progenitors (GNPs) in a Ras/Mapk-dependent manner.

Highlights • An extended postnatal phase of cerebellar hypoxia aids GNP proliferation via Hif1α • Hif1α controls CGN GZ exit and Pard complex function by activating Zeb1 expression • Hif1α-Zeb1 antagonism of Pard6α modulates Itgβ1 adhesion that promotes GZ occupancy • Hif1α control of polarity is a basis to dissect the pathology of hypoxic insults Summary Postnatal brain circuit assembly is driven by temporally regulated intrinsic and cell-extrinsic cues that organize neurogenesis, migration,...

4,455 Reads How we measure 'reads' A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more Skills and Expertise Mechanistic target of rapamycin (MTOR) cooperates with Hedgehog (HH) signaling, but the underlying mechanisms are incompletely understood.