Linked Life Data

11118883

Source:http://linkedlifedata.com/resource/pubmed/id/11118883

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-1-29
pubmed:abstractText
Patterning of the limb is coordinated by the complex interplay of three signaling regions: the apical ectodermal ridge (AER), the zone of polarizing activity (ZPA), and the non-ridge limb ectoderm. Complex feedback loops exist between Shh in the ZPA, Bmps and their antagonists in the adjacent mesenchyme, Wnt7a in the dorsal ectoderm and Fgfs in the AER. In contrast to the previously reported complete absence of digits in Shh(-/-) mice, we show that one morphologically distinct digit, with a well-delineated nail and phalanges, forms in Shh(-/-) hindlimbs, while intermediate structures are severely truncated and fused. The presence of distal autopod elements is consistent with weak expression of Hoxd13 in Shh(-/-) hindlimbs. Shh(-/-) forelimbs in contrast have one distal cartilage element, a less-well differentiated nail and fused intermediate bones. Interestingly, Ihh is expressed at the tip of Shh mutant limbs and could account for formation of distal structures. In contrast to previous studies we also demonstrate that Shh signaling is required for maintenance of normal Fgf8 expression, since expression of Fgf8, unlike some other AER marker genes, is rapidly lost from anterior to posterior after E10.5, with only a small domain of Fgf8 expression remaining posteriorly. Furthermore, loss of expanded Fgf8 expression is paralleled by a collapse of the handplate. Our data show that development of most intermediate elements of the hindlimb skeleton are Shh-dependent, and that Shh signaling is required for anterior-posterior expansion of the AER in both limbs and for the subsequent branching of zeugopod and autopod elements. Finally, we show that Shh is also required for outgrowth of the limb ectoderm and thus for the formation of a distinct limb compartment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0925-4773
pubmed:author
pubmed:issnType
Print
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
45-58
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11118883-Animals, pubmed-meshheading:11118883-Body Patterning, pubmed-meshheading:11118883-Cartilage, pubmed-meshheading:11118883-Extremities, pubmed-meshheading:11118883-Fibroblast Growth Factor 8, pubmed-meshheading:11118883-Fibroblast Growth Factors, pubmed-meshheading:11118883-Fibula, pubmed-meshheading:11118883-Hedgehog Proteins, pubmed-meshheading:11118883-Homeodomain Proteins, pubmed-meshheading:11118883-In Situ Hybridization, pubmed-meshheading:11118883-Mice, pubmed-meshheading:11118883-Mice, Inbred C57BL, pubmed-meshheading:11118883-Models, Biological, pubmed-meshheading:11118883-Mutation, pubmed-meshheading:11118883-Nails, pubmed-meshheading:11118883-Proteins, pubmed-meshheading:11118883-RNA, pubmed-meshheading:11118883-Tibia, pubmed-meshheading:11118883-Time Factors, pubmed-meshheading:11118883-Trans-Activators, pubmed-meshheading:11118883-Transcription Factors, pubmed-meshheading:11118883-beta-Galactosidase
pubmed:year
2001
pubmed:articleTitle
Some distal limb structures develop in mice lacking Sonic hedgehog signaling.
pubmed:affiliation
Ronald O. Perelman Department of Dermatology, New York University School of Medicine, NY, New York, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't