RGD Reference Report - Cellular mechanisms underlying the regulation of dendritic development by hepatocyte growth factor. - Rat Genome Database

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Cellular mechanisms underlying the regulation of dendritic development by hepatocyte growth factor.

Authors: Finsterwald, C  Martin, JL 
Citation: Finsterwald C and Martin JL, Eur J Neurosci. 2011 Oct;34(7):1053-61. doi: 10.1111/j.1460-9568.2011.07839.x. Epub 2011 Sep 6.
RGD ID: 9685161
Pubmed: PMID:21895802   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1460-9568.2011.07839.x   (Journal Full-text)

Acquisition of a mature dendritic morphology is critical for neural information processing. In particular, hepatocyte growth factor (HGF) controls dendritic arborization during brain development. However, the cellular mechanisms underlying the effects of HGF on dendritic growth remain elusive. Here, we show that HGF increases dendritic length and branching of rat cortical neurons through activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Activation of MAPK by HGF leads to the rapid and transient phosphorylation of cAMP response element-binding protein (CREB), a key step necessary for the control of dendritic development by HGF. In addition to CREB phosphorylation, regulation of dendritic growth by HGF requires the interaction between CREB and CREB-regulated transcription coactivator 1 (CRTC1), as expression of a mutated form of CREB unable to bind CRTC1 completely abolished the effects of HGF on dendritic morphology. Treatment of cortical neurons with HGF in combination with brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family that regulates dendritic development via similar mechanisms, showed additive effects on MAPK activation, CREB phosphorylation and dendritic growth. Collectively, these results support the conclusion that regulation of cortical dendritic morphology by HGF is mediated by activation of the MAPK pathway, phosphorylation of CREB and interaction of CREB with CRTC1.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Crtc1Ratpositive regulation of dendrite development  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Crtc1  (CREB regulated transcription coactivator 1)


Additional Information