Fig. 1.

Defining the thumb. The thumb domain is defined by the overlapping expression of HOXA13, TBX5, GLI3R, and HOXD13 and, importantly, an absence of other HOXD transcription factors. Before handplate formation (Carnegie Stg 15), TBX5 is expressed throughout the limb bud; however, as the handplate forms (Carnegie Stg 16), TBX5 expression extends into the presumptive thumb domain (boundary highlighted by yellow dashed lines), HOXA13 is induced, and a region adjacent to the presumptive thumb (PT), the foyer préaxiale primaire (fpp), undergoes programmed cell death (PCD). Processing of GLI3 by SHH sets up an AP gradient of GLI3 repressor (GLI3R) to GLI3 activator, respectively. SHH also regulates the patterning of the distal HOXD transcription factors (HOXD11–13) (Carnegie Stg 18) that physically interact with GLI3 to refine digit identity (the SHH-dependent boundary is highlighted by a purple dashed line). HOXD 10–12 have overlapping expression domains in presumptive digits 2 to 5 but are restricted from the thumb domain. In contrast, HOXD13 is expressed in all of the digit domains including the presumptive thumb. Note the corresponding embryonic days (e 11–13) of the mouse limb from whence these data have been derived.