RGD Reference Report - Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain. - Rat Genome Database

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Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain.

Authors: Sardi, SP  Murtie, J  Koirala, S  Patten, BA  Corfas, G 
Citation: Sardi SP, etal., Cell. 2006 Oct 6;127(1):185-97.
RGD ID: 5688294
Pubmed: PMID:17018285   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cell.2006.07.037   (Journal Full-text)

Embryonic multipotent neural precursors are exposed to extracellular signals instructing them to adopt different fates, neuronal or glial. However, the mechanisms by which precursors integrate these signals to make timely fate choices remained undefined. Here we show that direct nuclear signaling by a receptor tyrosine kinase inhibits the responses of precursors to astrocyte differentiation factors while maintaining their neurogenic potential. Upon neuregulin-induced activation and presenilin-dependent cleavage of ErbB4, the receptor's intracellular domain forms a complex with TAB2 and the corepressor N-CoR. This complex undergoes nuclear translocation and binds promoters of astrocytic genes, repressing their expression. Consistent with this observation, astrogenesis occurs precociously in ErbB4 knockout mice. Our studies define how presenilin-dependent nuclear signaling by a receptor tyrosine kinase directly regulates gene transcription and cell fate. This pathway could be of importance for neural stem cell biology and for understanding the pathogenesis of Alzheimer's disease.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPINcor1 (Rattus norvegicus)5688294 RGD 
protein binding  IPIErbb4 (Rattus norvegicus)5688294 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Erbb4  (erb-b2 receptor tyrosine kinase 4)
Ncor1  (nuclear receptor co-repressor 1)


Additional Information