Migration of Oligodendrocyte Progenitor Cells Is Controlled by Transforming Growth Factor beta Family Proteins during Corticogenesis

Abstract

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 Tgf beta 1 produced by the meninges and pericytes repelled ventral OPCs into the cortex at mouse embryonic stages. Ectopic activation of Bmp or Tgf beta 1 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 Tgf beta 1 or Bmp expression from mesenchymal cells. The data suggest that mesenchymal Tgf beta family proteins promote migration of ventral OPCs into the cortex during corticogenesis.