Early developmental arrest of mammalian limbs lacking HoxA/HoxD gene function.
Vertebrate HoxA and HoxD cluster genes are required for proper limb development. However, early lethality, compensation and redundancy have made a full assessment of their function difficult. Here we describe mice that are lacking all Hoxa and Hoxd functions in their forelimbs. We show that such limbs are arrested early in their developmental patterning and display severe truncations of distal elements, partly owing to the absence of Sonic hedgehog expression. These results indicate that the evolutionary recruitment of Hox gene function into growing appendages might have been crucial in implementing hedgehog signalling, subsequently leading to the distal extension of tetrapod appendages. Accordingly, these mutant limbs may be reminiscent of an ancestral trunk extension, related to that proposed for arthropods.
Kmita
Marie
M
Department of Zoology and Animal Biology and National Research Centre Frontiers in Genetics, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
Tarchini
Basile
B
Zàkàny
Jozsef
J
Logan
Malcolm
M
Tabin
Clifford J
CJ
Duboule
Denis
D
D000818:Animals; D019521:Body Patterning; D005552:Forelimb / Q000196:embryology*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D005810:Multigene Family / Q000235:genetics; D015398:Signal Transduction; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D015534:Trans-Activators