Mammalian inscuteable regulates spindle orientation and cell fate in the developing retina

Mihaela Žigman, Michel Cayouette, Christoforos Charalambous, Alexander Schleiffer, Oliver Hoeller, Dara Dunican, Christopher R. McCudden, Nicole Firnberg, Ben A. Barres, David P. Siderovski, Juergen A. Knoblich

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

During mammalian neurogenesis, progenitor cells can divide with the mitotic spindle oriented parallel or perpendicular to the surface of the neuroepithelium. Perpendicular divisions are more likely to be asymmetric and generate one progenitor and one neuronal precursor. Whether the orientation of the mitotic spindle actually determines their asymmetric outcome is unclear. Here, we characterize a mammalian homolog of Inscuteable (mInsc), a key regulator of spindle orientation in Drosophila. mInsc is expressed temporally and spatially in a manner that suggests a role in orienting the mitotic spindle in the developing nervous system. Using retroviral RNAi in rat retinal explants, we show that downregulation of mInsc inhibits vertical divisions. This results in enhanced proliferation, consistent with a higher frequency of symmetric divisions generating two proliferating cells. Our results suggest that the orientation of neural progenitor divisions is important for cell fate specification in the retina and determines their symmetric or asymmetric outcome.

Original languageEnglish
Pages (from-to)539-545
Number of pages7
JournalNeuron
Volume48
Issue number4
DOIs
StatePublished - 23 Nov 2005

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