Genetical studies on the skeleton of the mouse XXV. The Development of Syndactylism

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Abstract
1. The earliest manifestations of the gene for syndactylism discovered include hyperplasia of the apical ectodermal ridge of the limbs and hyperplasia of parts of the limb epidermis (10–10½-day stage). Somewhat later, a similar hyperplasia of the epidermis in the distal parts of the tail is found in some sm/sm embryos.2. Enlargement and deformation of the foot plates in both fore and hind limbs is present in the 12-day stage; in the fore limbs it probably starts on the preceding day. The foot plates are bent over in a palmar or plantar direction respectively; the crowding together of the middle digits thus produced is the mechanical cause of syndactylism.3. It is suggested that the enlargement of the foot plates with the ensuing deformities is due to increased stimulation of mesenchymal growth by the hyperplastic apical ectodermal ridge. On this interpretation, all the skeletal effects (including those in the tail) are secondary to a systemic tendency to epidermal hyperplasia.4. The hyperplastic regions of the apical ectodermal ridge and of the limb epidermis start to keratinize (parakeratosis) in the 13-day stage whereas in normal development keratinization of the skin does not start until some 3 days later.