Plexin-B2 controls the development of cerebellar granule cells.
Cerebellar granule cell progenitors proliferate postnatally in the upper part of the external granule cell layer (EGL) of the cerebellum. Postmitotic granule cells differentiate and migrate, tangentially in the EGL and then radially through the molecular and Purkinje cell layers. The molecular control of the transition between proliferation and differentiation in cerebellar granule cells is poorly understood. We show here that the transmembrane receptor Plexin-B2 is expressed by proliferating granule cell progenitors. To study Plexin-B2 function, we generated a targeted mutation of mouse Plexin-B2. Most Plexin-B2(-/-) mutants die at birth as a result of neural tube closure defects. Some mutants survive but their cerebellum cytoarchitecture is profoundly altered. This is correlated with a disorganization of the timing of granule cell proliferation and differentiation in the EGL. Many differentiated granule cells migrate inside the cerebellum and keep proliferating. These results reveal that Plexin-B2 controls the balance between proliferation and differentiation in granule cells.
Friedel
Roland H
RH
Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
Kerjan
Géraldine
G
Rayburn
Helen
H
Schüller
Ulrich
U
Sotelo
Constantino
C
Tessier-Lavigne
Marc
M
Chédotal
Alain
A
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D009419:Nerve Tissue Proteins; C519231:Plxnb2 protein, mouse; D011956:Receptors, Cell Surface