Layering defect in p35 deficiency is linked to improper neuronal-glial interaction in radial migration.
Several genes essential for neocortical layering have been identified in recent years, but their precise roles in this process remain to be elucidated. Mice deficient in p35--an activator of cyclin-dependent kinase 5 (Cdk5)--are characterized by a neocortex that has inverted layering. To decipher the physiological mechanisms that underlie this defect, we compared time-lapse recordings between p35(-/-) and wild-type cortical slices. In the p35(-/-) neocortex, the classic modes of radial migration--somal translocation and locomotion--were largely replaced by a distinct mode of migration: branched migration. Branched migration is cell-autonomous, associated with impaired neuronal-glial interaction and rare in neurons of scrambler mice, which are deficient in Dab1. Hence, our findings suggest that inside-out layering requires distinct functions of Reelin and p35/Cdk5 signaling, with the latter being important for proper glia-guided migration.
Gupta
Amitabh
A
Department of Pathology, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
Sanada
Kamon
K
Miyamoto
David T
DT
Rovelstad
Susan
S
Nadarajah
Bagirathy
B
Pearlman
Alan L
AL
Brunstrom
Jan
J
Tsai
Li-Huei
LH
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D000091042:Reelin Protein
D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C089495:neuronal Cdk5 activator (p25-p35); C000717128:Reln protein, mouse