Size of Baculum. As in many rodent and in some other mammalian species, male mice have a bone in their penis. This baculum (os priapi) originates from cells strongly expressing posterior
HoxD genes during development, which led to the proposal that limb and genital buds had similar developmental strategies in which posterior
Hox genes were essential components (
24). Furthermore, this small bone was slightly altered, because of a cellular deficit, in mice lacking
Hoxd-13 function (
3). We therefore looked for further baculum size reduction in these various compound genotypes.
The functional cooperation of the same four genes was clearly observed (Fig.
3). Whereas the inactivation of
Hoxd-13 led to a minor localized alteration of the baculum, the simultaneous inactivation of
Hoxd-11,
Hoxd-12, and
Hoxd-13 (
HoxDDel/Del) resulted in an overall size reduction of the bone and indeed of the entire organ. The functional input from
Hoxa-13 was best evidenced in
HoxDDel/+;
Hoxa-13+/− males, and an almost complete agenesis of the baculum was seen in
HoxDDel/Del;
Hoxa-13+/− (Fig.
3A). The remarkably similar functional cooperation of the same four genes during both digit and genital eminence development reflects the coexpression of
Hoxd-11,
Hoxd-12,
Hoxd-13, and
Hoxa-13 in overlapping domains of both developing autopods and external genitalia. It suggests that these apparently different structures share important developmental mechanisms, perhaps as a consequence of a common phylogenetic history (
18).