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Hand Surg Rehabil. 2018 Oct;37(5):265-274. doi: 10.1016/j.hansur.2018.03.007. Epub 2018 Jul 21.

Developmental biology of the upper limb.

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Institut de la Main, Clinique Bizet, 22, rue Georges-Bizet, 75116 Paris, France; Hôpital Necker-Enfants-Malades, 149, rue de Sèvres, 75015 Paris, France. Electronic address:


This article aims to provide hand surgeons with current knowledge on the developmental biology of the upper limb. It will review positioning, limb bud emergence and formation of the apical ectodermal ridge. The development of the limb bud is analyzed in its three axes: proximal-distal, anteroposterior and dorsoventral. The signaling center and primary morphogens that initiate and stimulate the development of each axis will be described. For the proximal-distal axis, the apical ectodermal ridge stimulates the production of FGFs in the underlying distal mesoderm. The anteroposterior (or radio-ulnar) differentiation is a function of the zone of polarizing activity via the small Sonic hedgehog protein, which diffuses in a decreasing concentration gradient from the ulnar to the radial side of the bud. This gradient is essential to digit identity and numbers. For the dorsoventral differentiation, the signaling center is the dorsal ectoderm, which secretes WNT7A. Limb segmentation is described in three parts (arm, forearm and hand) along with the formation of the digital rays until finger separation. An example of congenital anomalies is provided for each step. To keep the length of this lecture within reason, the embryogenesis of nerves, blood vessels, muscles and tendons will not be discussed. On the other hand, the singularity of the thumb relative to the other fingers will be described. With a better understanding of developmental biology, surgeons should have better insight into congenital anomalies of the upper limb. This approach is the basis for the new OMT classification used by the IFFSH.


BMP; Biologie moléculaire; Congenital anomaly; Gènes HOX; HOX genes; Hand; Main; Malformation congénitale; Membre supérieur; Molecular Biology; Morphogenesis; Morphogenèse; Sonic hedgehog; Upper limb; WNT

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