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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-1-14
pubmed:abstractText
Fibroblast growth factors (FGFs) are signals from the apical ectodermal ridge (AER) that are essential for limb pattern formation along the proximodistal (PD) axis. However, how patterning along the PD axis is regulated by AER-FGF signals remains controversial. To further explore the molecular mechanism of FGF functions during limb development, we conditionally inactivated fgf receptor 2 (Fgfr2) in the mouse AER to terminate all AER functions; for comparison, we inactivated both Fgfr1 and Fgfr2 in limb mesenchyme to block mesenchymal AER-FGF signaling. We also re-examined published data in which Fgf4 and Fgf8 were inactivated in the AER. We conclude that limb skeletal phenotypes resulting from loss of AER-FGF signals cannot simply be a consequence of excessive mesenchymal cell death, as suggested by previous studies, but also must be a consequence of reduced mesenchymal proliferation and a failure of mesenchymal differentiation, which occur following loss of both Fgf4 and Fgf8. We further conclude that chondrogenic primordia formation, marked by initial Sox9 expression in limb mesenchyme, is an essential component of the PD patterning process and that a key role for AER-FGF signaling is to facilitate SOX9 function and to ensure progressive establishment of chondrogenic primordia along the PD axis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
135
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
483-91
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18094024-Animals, pubmed-meshheading:18094024-Body Patterning, pubmed-meshheading:18094024-Bone and Bones, pubmed-meshheading:18094024-Cell Death, pubmed-meshheading:18094024-Cell Differentiation, pubmed-meshheading:18094024-Cell Proliferation, pubmed-meshheading:18094024-Ectoderm, pubmed-meshheading:18094024-Embryo, Mammalian, pubmed-meshheading:18094024-Fibroblast Growth Factors, pubmed-meshheading:18094024-Gene Expression Regulation, Developmental, pubmed-meshheading:18094024-Integrases, pubmed-meshheading:18094024-Limb Buds, pubmed-meshheading:18094024-Mesoderm, pubmed-meshheading:18094024-Mice, pubmed-meshheading:18094024-Phenotype, pubmed-meshheading:18094024-Receptor, Fibroblast Growth Factor, Type 1, pubmed-meshheading:18094024-Receptor, Fibroblast Growth Factor, Type 2, pubmed-meshheading:18094024-Signal Transduction
pubmed:year
2008
pubmed:articleTitle
FGF signaling regulates mesenchymal differentiation and skeletal patterning along the limb bud proximodistal axis.
pubmed:affiliation
Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110 USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural