TY - JOUR
T1 - Mammalian inscuteable regulates spindle orientation and cell fate in the developing retina
AU - Žigman, Mihaela
AU - Cayouette, Michel
AU - Charalambous, Christoforos
AU - Schleiffer, Alexander
AU - Hoeller, Oliver
AU - Dunican, Dara
AU - McCudden, Christopher R.
AU - Firnberg, Nicole
AU - Barres, Ben A.
AU - Siderovski, David P.
AU - Knoblich, Juergen A.
N1 - Funding Information:
We want to thank Ciara Gallagher, Maria Novatchkova, Sarah K. Bowman, Masakazu Yamazaki, and Maria Pia Postiglione for critically reading the manuscript; Karin Paiha and Pawel Pasierbek for help with microscopy; Christine Jolicoueur for technical assistance; Hartmut Beug, Ian Macara, and the Developmental Studies Hybridoma Bank for reagents. Work in J.A.K.'s lab is supported by the Austrian Academy of Sciences and the Austrian Research Fund (FWF). Work in M.C.'s lab is funded by the Canadian Institute of Health Research. Work in D.P.S.'s lab is funded by NIH grants R01 GM062338 and P01 GM065533. Work in B.A.B.'s lab is funded by NIH grant NEI R01 EY11310.
PY - 2005/11/23
Y1 - 2005/11/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=27844471177&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2005.09.030
DO - 10.1016/j.neuron.2005.09.030
M3 - Article
C2 - 16301171
AN - SCOPUS:27844471177
SN - 0896-6273
VL - 48
SP - 539
EP - 545
JO - Neuron
JF - Neuron
IS - 4
ER -