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Dev Cell. 2012 Oct 16;23(4):729-44.
p27(Kip1) is a microtubule-associated protein that
promotes microtubule polymerization during neu-
ron migration.
Godin JD, Thomas N, Laguesse S, Malinouskaya L, Close P, Malaise O, Purnelle A, Raineteau O,
Campbell K, Fero M, Moonen G, Malgrange B, Chariot A, Metin C, Besson A, Nguyen L.
Abstract
The migration of cortical interneurons is characterized by extensive morphological changes
that result from successive cycles of nucleokinesis and neurite branching. Their molecular
bases remain elusive, and the present work describes how p27(Kip1) controls cell-cycle-
unrelated signaling pathways to regulate these morphological remodelings. Live imaging
reveals that interneurons lacking p27(Kip1) show delayed tangential migration resulting
from defects in both nucleokinesis and dynamic branching of the leading process. At the
molecular level, p27(Kip1) is a microtubule-associated protein that promotes polymeriza-
tion of microtubules in extending neurites, thereby contributing to tangential migration.
Furthermore, we show that p27(Kip1) controls actomyosin contractions that drive both
forward translocation of the nucleus and growth cone splitting. Thus, p27(Kip1) cell-auto-
nomously controls nucleokinesis and neurite branching by regulating both actin and micro-
tubule cytoskeletons.
Coronal section through a the brain of a mouse
embryo showing the expression of p27 (red) in
cortical interneurons (green).
p27 (green) interacts with the small GT-
Pase RhoA (red) in actin-enriched (blue)
domains in interneurons.
P27 (green) localises along microtubules (tubulin in red) in a
migrating interneuron
Molecular mechanisms downstream
p27 that regulate tangential migration
of cortical interneurons. p27 control
two distinct signalling pathways that
promote the remodelling of important
cytoskeleton components, the actin (red)
or the microtubules (green).
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