Bmp2, Bmp4 and Bmp7 are co-required in the mouse AER for normal digit patterning but not limb outgrowth.
Outgrowth and patterning of the vertebrate limb requires a functional apical ectodermal ridge (AER). The AER is a thickening of ectodermal tissue located at the distal end of the limb bud. Loss of this structure, either through genetic or physical manipulations results in truncation of the limb. A number of genes, including Bmps, are expressed in the AER. Previously, it was shown that removal of the BMP receptor Bmpr1a specifically from the AER resulted in complete loss of hindlimbs suggesting that Bmp signaling in the AER is required for limb outgrowth. In this report, we genetically removed the three known AER-expressed Bmp ligands, Bmp2, Bmp4 and Bmp7 from the AER of the limb bud using floxed conditional alleles and the Msx2-cre allele. Surprisingly, only defects in digit patterning and not limb outgrowth were observed. In triple mutants, the anterior and posterior AER was present but loss of the central region of the AER was observed. These data suggest that Bmp ligands expressed in the AER are not required for limb outgrowth but instead play an essential role in maintaining the AER and patterning vertebrate digits.
Department of Molecular Genetics and Microbiology and the Genetics Institute, University of Florida, College of Medicine, Gainesville, Florida, United States of America.
Kyung-Suk
KS
Choi
Chanmi
C
Lee
Danielle M
DM
Maatouk
Brian D
BD
Harfe
D000483:Alleles; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics*; D005121:Extremities / Q000196:embryology*; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D018878:Limb Buds / Q000254:growth & development*; D017880:Limb Deformities, Congenital / Q000235:genetics; D051957:MSX1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D051957:MSX1 Transcription Factor; C084119:MSX2 protein; D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D051524:Fibroblast Growth Factor 8