BMPs inhibit neurogenesis by a mechanism involving degradation of a transcription factor.
Bone morphogenetic proteins (BMPs), negative regulators of neural determination in the early embryo, were found to be potent inhibitors of neurogenesis in olfactory epithelium (OE) cultures. BMPs 2, 4 or 7 decreased the number of proliferating progenitor cells and blocked production of olfactory receptor neurons (ORNs). Experiments suggested that this effect was due to an action of BMPs on an early-stage progenitor in the ORN lineage. Further analysis revealed that progenitors exposed to BMPs rapidly (< 2 h) lost MASH1, a transcription factor known to be required for the production of ORNs. This disappearance was due to proteolysis of existing MASH1 protein, but new gene expression was required to trigger it. The data suggest a novel mechanism of BMP action, whereby the induced degradation of an essential transcription factor results in premature termination of a neuronal lineage.
Shou
J
J
Department of Anatomy & Neurobiology and the Developmental Biology Center, University of California Irvine, College of Medicine, 92697-1275, USA.
Rim
P C
PC
Calof
A L
AL
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D003114:Colony-Forming Units Assay; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D009097:Multienzyme Complexes / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta
D051792:Basic Helix-Loop-Helix Proteins; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D017077:Culture Media, Conditioned; D003546:Cysteine Endopeptidases; D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; D046988:Proteasome Endopeptidase Complex; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C499317:Ascl1 protein, mouse; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse