Mammalian inscuteable regulates spindle orientation and cell fate in the developing retina.
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.
Zigman
Mihaela
M
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3-5, 1030 Vienna, Austria.
Cayouette
Michel
M
Charalambous
Christoforos
C
Schleiffer
Alexander
A
Hoeller
Oliver
O
Dunican
Dara
D
McCudden
Christopher R
CR
Firnberg
Nicole
N
Barres
Ben A
BA
Siderovski
David P
DP
Knoblich
Juergen A
JA
D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology; D019143:Evolution, Molecular; D051379:Mice; D041681:NIH 3T3 Cells; D009474:Neurons / Q000166:cytology; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D010786:Photoreceptor Cells / Q000166:cytology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D008941:Spindle Apparatus / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology
D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D009479:Neuropeptides; C098678:insc protein, Drosophila