Linked Life Data

19699733

Source:http://linkedlifedata.com/resource/pubmed/id/19699733

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-10-19
pubmed:abstractText
Muscle stem cells and their progeny play a fundamental role in the regeneration of adult skeletal muscle. We have previously shown that activation of the canonical Wnt/beta-catenin signaling pathway in adult myogenic progenitors is required for their transition from rapidly dividing transient amplifying cells to more differentiated progenitors. Whereas Wnt signaling in Drosophila is dependent on the presence of the co-regulator Legless, previous studies of the mammalian ortholog of Legless, BCL9 (and its homolog, BCL9-2), have not revealed an essential role of these proteins in Wnt signaling in specific tissues during development. Using Cre-lox technology to delete BCL9 and BCL9-2 in the myogenic lineage in vivo and RNAi technology to knockdown the protein levels in vitro, we show that BCL9 is required for activation of the Wnt/beta-catenin cascade in adult mammalian myogenic progenitors. We observed that the nuclear localization of beta-catenin and downstream TCF/LEF-mediated transcription, which are normally observed in myogenic progenitors upon addition of exogenous Wnt and during muscle regeneration, were abrogated when BCL9/9-2 levels were reduced. Furthermore, reductions of BCL9/9-2 inhibited the promotion of myogenic differentiation by Wnt and the normal regenerative response of skeletal muscle. These results suggest a critical role of BCL9/9-2 in the Wnt-mediated regulation of adult, as opposed to embryonic, myogenic progenitors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1095-564X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
335
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
93-105
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed-meshheading:19699733-Animals, pubmed-meshheading:19699733-Cell Differentiation, pubmed-meshheading:19699733-Cell Lineage, pubmed-meshheading:19699733-Cells, Cultured, pubmed-meshheading:19699733-Drosophila Proteins, pubmed-meshheading:19699733-Humans, pubmed-meshheading:19699733-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:19699733-Mice, pubmed-meshheading:19699733-Mice, Knockout, pubmed-meshheading:19699733-Muscle, Skeletal, pubmed-meshheading:19699733-Muscle Development, pubmed-meshheading:19699733-Neoplasm Proteins, pubmed-meshheading:19699733-RNA Interference, pubmed-meshheading:19699733-Regeneration, pubmed-meshheading:19699733-Signal Transduction, pubmed-meshheading:19699733-Stem Cells, pubmed-meshheading:19699733-Wnt Proteins, pubmed-meshheading:19699733-beta Catenin
pubmed:year
2009
pubmed:articleTitle
BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration.
pubmed:affiliation
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305-5235, USA. brack.andrew@mgh.harvard.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural