Digital development and morphogenesis

Abstract

Signalling interactions between the polarizing region, which produces SHH, and the apical ectodermal ridge, which produces FGFs, are essential for outgrowth and patterning of vertebrate limbs. However, mechanisms that mediate translation of early positional information of cells into anatomy remain largely unknown. In particular, the molecular and cellular basis of digit morphogenesis are not fully understood, either in terms of the formation of the different digits along the antero-posterior axis or in the way digits stop growing once pattern formation has been completed. Here we will review recent data about digit development. Manipulation of morphogenetic signals during digit formation, including application of SHH interdigitally, has shown that digit primordia possess a certain plasticity, and that digit anatomy becomes irreversibly fixed during morphogenesis. The process of generation of joints and thus segmentation and formation of digit tips is also discussed.

Fig. 1

Alcian Blue-stained chick limb buds at early stages in digit formation. First metacarpo/metatarso-phalangeal joints (asterisks) and digit/toe condensations (arrows) appear in the most posterior rays. R, radius; U, ulna; mc, metacarpal bone; dc, digital condensation; T, tibia; F, fibula; mt, metatarsal bone; tc, toe condensation.

Fig. 2

Series of Alcian Blue-stained chick leg buds showing sequential appearance of joints and phalanges in toes. Continuous distal cartilage condensations become segmented by generation of a joint. From stage 29 to stage 34 represents about 3 days of development.

Fig. 3

Stage 36 (10 days incubation) chick embryo leg stained for cartilage with Alcian Blue. Completed toes can be seen with phalanges, joints and tips, which will bear claws. Numbers refer to identity of toes, from anterior (1 = big toe) to posterior (4). Note increasing number of phalanges in more posterior toes.

Fig. 4

Application of beads soaked in SHH to the interdigital spaces leads to generation of longer digits with extra phalanges (arrow) and joint (arrowhead). Asterisk marks position of SHH-soaked bead.

Fig. 5

Ectopic extra digit (arrow) induced in the interdigital space of a chick embryo leg bud by application of sn SHH-soaked bead (asterisk). Note that extra digit contains a distal phalange and tip.

Fig. 6

Stage 35 chick leg bud showing expression (arrow) of Gdf5 by whole-mount in situ hybridization. Note intense staining of all interphalangeal joints as well as metacarpo-phalangeal joints.