How is the thumb different?
The earliest trace of a difference between the future thumb and the other digits is the expression of a subfamily of Hox genes, the AbdB-related group of Hox genes in the D cluster. Hox genes code for transcription factors, and most jawed vertebrates (with the exception of teleost (bony) fishes) have the Hox genes in four tightly linked clusters, called A, B, C and D [2]. Each gene cluster has the same 3′ to 5′ arrangement of corresponding genes, with those determining digit identity located at the 5′ end of the cluster. In the embryo, the future hand or foot expresses four of these genes – HoxD-13, HoxD-12, HoxD-11 and HoxD-10 [3]. The embryonic territories in which digits 2 to 5 develop express all four genes, whereas the thumb develops from a territory where only HoxD-13 is expressed. There is much evidence that this association between the absence of HoxD-12 to HoxD-10 expression and thumb identity is causally important. Misexpression of HoxD-12 [4] or HoxD-11 [5] in the digit 1 te
