Linked Life Data

14623241

Source:http://linkedlifedata.com/resource/pubmed/id/14623241

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-11-18
pubmed:abstractText
Limb skeletal muscle is derived from cells of the dermomyotome that detach and migrate into the limb buds to form separate dorsal and ventral myogenic precursor domains. Myogenic precursor cell migration is dependent on limb bud mesenchymal expression of hepatocyte growth factor/scatter factor (Hgf), which encodes a secreted ligand that signals to dermomyotome through the membrane receptor tyrosine kinase Met. Here, we find that correct patterning of Hgf expression in forelimb buds is dependent on retinoic acid (RA) synthesized by retinaldehyde dehydrogenase 2 (Raldh2) expressed proximally. Raldh2(-/-) forelimb buds lack RA and display an anteroproximal shift in expression of Hgf such that its normally separate dorsal and ventral expression domains are joined into a single anterior-proximal domain. Met and MyoD are expressed in this abnormal domain, indicating that myogenic cell migration and differentiation are occurring in the absence of RA, but in an abnormal location. An RA-reporter transgene revealed that RA signaling in the forelimb bud normally exists in a gradient across the proximodistal axis, but uniformly across the anteroposterior axis, with all proximal limb bud cells exhibiting activity. Expression of Bmp4, an inhibitor of Hgf expression, is increased and shifted anteroproximally in Raldh2(-/-) limb buds, thus encroaching into the normal expression domain of Hgf. Our studies suggest that RA signaling provides proximodistal information for limb buds that counterbalances Bmp signaling, which in turn helps mediate proximodistal and anteroposterior patterning of Hgf expression to correctly direct migration of Met-expressing myogenic precursor cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0012-1606
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
264
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
191-201
pubmed:dateRevised
2010-7-27
pubmed:meshHeading
pubmed-meshheading:14623241-Aldehyde Oxidoreductases, pubmed-meshheading:14623241-Animals, pubmed-meshheading:14623241-Animals, Genetically Modified, pubmed-meshheading:14623241-Body Patterning, pubmed-meshheading:14623241-Bone Morphogenetic Protein 4, pubmed-meshheading:14623241-Bone Morphogenetic Proteins, pubmed-meshheading:14623241-Chick Embryo, pubmed-meshheading:14623241-Forelimb, pubmed-meshheading:14623241-Hedgehog Proteins, pubmed-meshheading:14623241-Hepatocyte Growth Factor, pubmed-meshheading:14623241-In Situ Hybridization, pubmed-meshheading:14623241-Limb Buds, pubmed-meshheading:14623241-Morphogenesis, pubmed-meshheading:14623241-Muscle Development, pubmed-meshheading:14623241-Myoblasts, pubmed-meshheading:14623241-Proto-Oncogene Proteins c-met, pubmed-meshheading:14623241-Retinal Dehydrogenase, pubmed-meshheading:14623241-Signal Transduction, pubmed-meshheading:14623241-Trans-Activators, pubmed-meshheading:14623241-Tretinoin
pubmed:year
2003
pubmed:articleTitle
Patterning of forelimb bud myogenic precursor cells requires retinoic acid signaling initiated by Raldh2.
pubmed:affiliation
OncoDevelopmental Biology Program, Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.