[Abstract Title]. - Society for Neuroscience

in Netrin-1 -/- and DCC-KO were multipolar instead of bipolar, suggesting that SPN use a different mode of migration when commissural fibers
are absent. Thus Netrin may affect SPN migration through its effect on commissural fiber guidance.
Disclosures: J.W. Yip , None; S. Sasaki, None; K. Nakajima, None.
Poster
230. Cell Migration: Molecules Mediating Migration
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 230.19/B9
Topic: A.02.c. Cell migration
Support: ANR-06-NEUR-010
EU FP7-2007-ICT-216593 (SECO)
Title: Role of p27kip1 in modulating radial migration in the neocortex
Authors: *E. GAUTIER 1,2 , N. DOERFLINGER 1,2 , V. CORTAY 1,2 , C. HUISSOUD 3 , P.
GIROUD 1,2 , M. BERLAND 4 , H. KENNEDY 1,2 , C. DEHAY 1,2 ;
1 Inserm, U846, Stem Cell and Brain Res. Inst., BRON, France; 2 Univ. de Lyon, Lyon 1, UMR-S
846, Lyon, France; 3 Hospices civils de Lyon, Hôpital de la Croix-Rousse, Lyon, France;
4 Hospices civils de Lyon, Hôpital Lyon Sud, Pierre-Benite, France
Abstract: Projection neuron precursors proliferate in the ventricular and subventricular zones,
before migrating radially towards their final destination in the cortical plate. The cytoarchitecture
of the neocortex depends crucially on the coordination of the rates of proliferation and migration.
p27kip1is a putative candidate for coordinating proliferation and migration of cortical neurons
(Nguyen et al., 2006). p27kip1 is a modular protein: via its N-term domain, it binds to the
cyclin/Cdk complexes in the nucleus and inhibits the G1/S phase transition, whereas via its Cterm
domain, it inhibits RhoA in the cytoplasm and so promotes cellular migration. Using gain
of function (GOF) and downmodulation (DM) experiments based on electroporation of plasmids
and siRNAs respectively in E15 mouse cortical precursors, we have explored the role of p27kip1
on radial migration in the cortex. Immunohistochemistry and time-lapse videorecordings (TLV)
on organotypic slices show that overexpression of p27kip1 leads to a decrease in the rate of
proliferation and importantly to an increase in the speed of migration, whereas a
downmodulation of p27kip1 by RNA interference gives the opposite results. Variations in the
speed of migration are correlated with modulations of the expression level of cytoplasmic
p27kip1 in migrating neurons.
In the E77 -E80 monkey, the rate of proliferation in visual area A17 is higher than in area 18.