Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Abnormal development of the apical ectodermal ridge and polysyndactyly in Megf7-deficient mice.

Human molecular genetics | Nov 15, 2005

Megf7/Lrp4 is a member of the functionally diverse low-density lipoprotein receptor gene family, a class of ancient and highly conserved cell surface receptors with broad functions in cargo transport and cellular signaling. To gain insight into the as yet unknown biological role of Megf7/Lrp4, we have disrupted the gene in mice. Homozygous Megf7-deficient mice are growth-retarded, with fully penetrant polysyndactyly in their fore and hind limbs, and partially penetrant abnormalities of tooth development. The reason for this developmental abnormality is apparent as early as embryonic day 9.5 when the apical ectodermal ridge (AER), the principal site of Megf7 expression at the distal edge of the embryonic limb bud, forms abnormally in the absence of Megf7. Ectopic expression and aberrant signaling of several molecules involved in limb patterning, including Fgf8, Shh, Bmp2, Bmp4 and Wnt7a, as well as the Wnt- and Bmp-responsive transcription factors Lmx1b and Msx1, result in reduced apoptosis and symmetrical dorsal and ventral expansions of the AER. Abnormal signaling from the AER precedes ectopic chondrocyte condensation and subsequent fusion and duplication of digits in the Megf7 knockouts. Megf7 can antagonize canonical Wnt signaling in vitro. Taken together, these findings are consistent with a role of Megf7 as a modulator of cellular signaling pathways involving Wnts, Bmps, Fgfs and Shh. A similar autosomal recessive defect may also occur in man, where polysyndactyly, in combination with craniofacial abnormalities, is also part of a common genetic syndrome.

Pubmed ID: 16207730 RIS Download

Mesh terms: Animals | Body Weight | Bone Morphogenetic Proteins | Ectoderm | Fibroblast Growth Factors | Hedgehog Proteins | Mice | Mice, Knockout | Receptors, LDL | Signal Transduction | Syndactyly | Trans-Activators | Wnt Proteins | Wnt1 Protein

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NHLBI NIH HHS, Id: R37 HL063762
  • Agency: NHLBI NIH HHS, Id: HL20948
  • Agency: NHLBI NIH HHS, Id: HL63762
  • Agency: NINDS NIH HHS, Id: NS43408

Comparative Toxicogenomics Database (Data, Disease Annotation)

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.