Review of the Molecular Development of the Thumb: Digit Primera

BACKGROUND: The thumb, or digit 1, is not a typical digit. In addition to its unusual mobility and function, its formation is also unusual. It is the last digit to form and the most commonly targeted when limb development is disrupted. The thumb domain is defined by the overlapping expression of HOXA13, TBX5, GLI3R, and HOXD13 and, importantly, by an absence of other distal HOXD transcription factors. This brief review, combining developmental biology and clinical genetics, discusses the current understanding of how the thumb domain is established.