Although many of the genes involved in limb development have been identified, little is known about their transcriptional regulation. On p. 4581, Knosp and co-workers report that HOXA13, a transcription factor whose absence causes developmental defects in mammalian digits and interdigital tissue, controls distal limb morphogenesis by directly regulating the expression of bone morphogenetic proteins (BMPs) 2 and 7. The researchers show first that Bmp2, Bmp7 and Hoxa13 are co-expressed during normal mouse limb development, and that absence of functional HOXA13 reduces Bmp2 and Bmp7 expression in the affected limb tissues. Then, they identify and characterise enhancer regions in Bmp2 and Bmp7 that interact with the HOXA13 DNA-binding domain in vitro and in vivo. Finally, they show that exogenously applied BMP2 or BMP7 partly rescues the Hoxa13 mutant limb phenotype. These results thus identify an important mechanistic link between two well-characterised families of developmental factors.
- © 2004.
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