Highlights d An extended postnatal phase of cerebellar hypoxia aids GNP proliferation via Hif1a d Hif1a controls CGN GZ exit and Pard complex function by activating Zeb1 expression d Hif1a-Zeb1 antagonism of Pard6a modulates Itgb1 adhesion that promotes GZ occupancy d Hif1a control of polarity is a basis to dissect the pathology of hypoxic insults

Cerebellar granule neurons (CGNs) exploit Bergmann glia (BG) fibres for radial migration, and cell-cell contacts have a pivotal role in this process. Nevertheless, little is known about the mechanisms that control CGN-BG interaction. Here we demonstrate that the actin-binding protein profilin1 is essential for CGN-glial cell adhesion and radial migration. Profilin1 ablation from mouse brains leads to a cerebellar hypoplasia, aberrant organization of cerebellar cortex layers and ectopic CGNs. Conversely, neuronal progenitor proliferation, tangential migration of neurons and BG morphology appear to be independent of profilin1. Our mouse data and the mapping of developmental neuropathies to the chromosomal region of PFN1 suggest a similar function for profilin1 in humans.

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