Gene deletion mutants reveal a role for semaphorin receptors of the plexin-B family in mechanisms underlying corticogenesis.
Semaphorins and their receptors, plexins, are emerging as key regulators of various aspects of neural and nonneural development. Semaphorin 4D (Sema4D) and B-type plexins demonstrate distinct expression patterns over critical time windows during the development of the murine neocortex. Here, analysis of mice genetically lacking plexin-B1 or plexin-B2 revealed the significance of Sema4D-plexin-B signaling in cortical development. Deficiency of plexin-B2 resulted in abnormal cortical layering and defective migration and differentiation of several subtypes of cortical neurons, including Cajal-Retzius cells, GABAergic interneurons, and principal cells in vivo. In contrast, a lack of plexin-B1 did not impact on cortical development in vivo. In various ex vivo assays on embryonic forebrain, Sema4D enhanced the radial and tangential migration of developing neurons in a plexin-B2-dependent manner. These results suggest that Sema4D-plexin-B2 interactions regulate mechanisms underlying cell specification, differentiation, and migration during corticogenesis.
Hirschberg
A
A
Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Deng
S
S
Korostylev
A
A
Paldy
E
E
Costa
M R
MR
Worzfeld
T
T
Vodrazka
P
P
Wizenmann
A
A
Götz
M
M
Offermanns
S
S
Kuner
R
R
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics / Q000502:physiology; D019579:Neocortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D039961:Semaphorins / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics / Q000502:physiology
D009419:Nerve Tissue Proteins; C492118:Plxnb1 protein, mouse; C519231:Plxnb2 protein, mouse; D011956:Receptors, Cell Surface; C103150:Sema4d protein, mouse; D039961:Semaphorins