Regulation of number and size of digits by posterior Hox genes: A dose-dependent mechanism with potential evolutionary implications

J Zákány, C Fromental-Ramain… - Proceedings of the …, 1997 - National Acad Sciences
J Zákány, C Fromental-Ramain, X Warot, D Duboule
Proceedings of the National Academy of Sciences, 1997National Acad Sciences
The proper development of digits, in tetrapods, requires the activity of several genes of the
HoxA and HoxD homeobox gene complexes. By using a variety of loss-of-function alleles
involving the five Hox genes that have been described to affect digit patterning, we report
here that the group 11, 12, and 13 genes control both the size and number of murine digits
in a dose-dependent fashion, rather than through a Hox code involving differential
qualitative functions. A similar dose–response is observed in the morphogenesis of the …
The proper development of digits, in tetrapods, requires the activity of several genes of the HoxA and HoxD homeobox gene complexes. By using a variety of loss-of-function alleles involving the five Hox genes that have been described to affect digit patterning, we report here that the group 11, 12, and 13 genes control both the size and number of murine digits in a dose-dependent fashion, rather than through a Hox code involving differential qualitative functions. A similar dose–response is observed in the morphogenesis of the penian bone, the baculum, which further suggests that digits and external genitalia share this genetic control mechanism. A progressive reduction in the dose of Hox gene products led first to ectrodactyly, then to olygodactyly and adactyly. Interestingly, this transition between the pentadactyl to the adactyl formula went through a step of polydactyly. We propose that in the distal appendage of polydactylous short-digited ancestral tetrapods, such as Acanthostega, the HoxA complex was predominantly active. Subsequent recruitment of the HoxD complex contributed to both reductions in digit number and increase in digit length. Thus, transition through a polydactylous limb before reaching and stabilizing the pentadactyl pattern may have relied, at least in part, on asynchronous and independent changes in the regulation of HoxA and HoxD gene complexes.
National Acad Sciences