BMPR1a signaling determines numbers of oligodendrocytes and calbindin-expressing interneurons in the cortex.
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.
Samanta
Jayshree
J
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Burke
Gordon M
GM
McGuire
Tammy
T
Pisarek
Anna J
AJ
Mukhopadhyay
Abhishek
A
Mishina
Yuji
Y
Kessler
John A
JA
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D064026:Calbindins; D002452:Cell Count; D002453:Cell Cycle; D019070:Cell Lineage; D016922:Cellular Senescence; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D003643:Death; D007395:Interneurons / Q000145:classification / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins; D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D051785:Smad Proteins; D005680:gamma-Aminobutyric Acid; C494786:Olig1 protein, mouse; C498212:Bmpr1a protein, mouse