Journal
NATURE
Volume 435, Issue 7045, Pages 1113-1116Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature03648
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Funding
- Medical Research Council [MC_U117560477] Funding Source: Medline
- NICHD NIH HHS [R37 HD032443] Funding Source: Medline
- Medical Research Council [MC_U117560477] Funding Source: researchfish
- MRC [MC_U117560477] Funding Source: UKRI
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Vertebrate HoxA and HoxD cluster genes are required for proper limb development(1-3). However, early lethality, compensation and redundancy have made a full assessment of their function difficult(3-5). 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(6).
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