BMPR1a signaling determines numbers of oligodendrocytes and calbindin-expressing interneurons in the cortex

Jayshree Samanta, Gordon M. Burke, Tammy McGuire, Anna J. Pisarek, Abhishek Mukhopadhyay, Yuji Mishina, John A. Kessler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Progenitor cells that express the transcription factor olig1 generate several neural cell types including oligodendrocytes and GABAergic interneurons in the dorsal cortex. The fate of these progenitor cells is regulated by a number of signals including bone morphogenetic proteins (BMPs) secreted in the dorsal forebrain. BMPs signal by binding to heteromeric serine-threonine kinase receptors formed by type I (BMPR1a, BMPR1b, Alk2) and type II (BMPRII) subunits. To determine the specific role of the BMPR1a subunit in lineage commitment by olig1-expressing cells, we used a cre/loxP genetic approach to ablate BMPR1a in these cells while leaving signaling from other subunits intact. There was a reduction in numbers of immature oligodendrocytes in the BMPR1a-null mutant brains at birth. However, by postnatal day 20, the BMPR1a-null mice had a significant increase in the number of mature and immature oligodendrocytes compared with wild-type littermates. There was also an increase in the proportion of calbindin-positive interneurons in the dorsomedial cortex of BMPR1a-null mice at birth without any change in the number of parvalbumin- or calretinin-positive cells. These effects were attributable, at least in part, to a decrease in the length of the cell cycle in subventricular zone progenitor cells. Thus, our findings indicate that BMPR1a mediates the suppressive effects of BMP signaling on oligodendrocyte lineage commitment and on the specification of calbindin-positive interneurons in the dorsomedial cortex.

Original languageEnglish (US)
Pages (from-to)7397-7407
Number of pages11
JournalJournal of Neuroscience
Volume27
Issue number28
DOIs
StatePublished - Jul 11 2007

Keywords

  • BMPR1a
  • Calbindin
  • Knock-out mice
  • Olig1
  • Oligodendrocyte
  • Stem cell

ASJC Scopus subject areas

  • Neuroscience(all)

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