BMPs inhibit neurogenesis by a mechanism involving degradation of a transcription factor.

Abstract:

: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.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Shou J,Rim PC,Calof AL

doi

10.1038/7251

subject

Has Abstract

pub_date

1999-04-01 00:00:00

pages

339-45

issue

4

eissn

1097-6256

issn

1546-1726

journal_volume

2

pub_type

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