Migration of oligodendrocyte progenitor cells is controlled by transforming growth factor β family proteins during corticogenesis.
During embryonic development oligodendrocyte precursor cells (OPCs) are generated first in the ventral forebrain and migrate dorsally to occupy the cortex. The molecular cues that guide this migratory route are currently completely unknown. Here, we show that bone morphogenetic protein-4 (Bmp4), Bmp7, and Tgfβ1 produced by the meninges and pericytes repelled ventral OPCs into the cortex at mouse embryonic stages. Ectopic activation of Bmp or Tgfβ1 signaling before the entrance of OPCs into the cortex hindered OPC migration into the cortical areas. OPCs without Smad4 signaling molecules also failed to migrate into the cortex efficiently and formed heterotopia in ventral areas. OPC migration into the cortex was also dramatically reduced by conditional inhibition of Tgfβ1 or Bmp expression from mesenchymal cells. The data suggest that mesenchymal Tgfβ family proteins promote migration of ventral OPCs into the cortex during corticogenesis.
Department of Neurology, Korea Brain Research Institute, 700-010 Daegu, Korea.
Youngshik
Y
Choe
Department of Neurology.
Trung
T
Huynh
Department of Neurology, Programs in Neuroscience, Developmental Stem Cell Biology, and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research and University of California, San Francisco, San Francisco, California 94158 and sam.pleasure@ucsf.edu.
Samuel J
http://orcid.org/0000-0001-8599-1613
SJ
Pleasure
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism*; D008578:Meninges / Q000196:embryology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D055495:Neurogenesis; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D020286:Pericytes / Q000378:metabolism; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D053773:Transforming Growth Factor beta1; C525820:bmp7 protein, mouse