Saunders's framework for understanding limb development as a platform for investigating limb evolution

Abstract

John W. Saunders, Jr. made seminal discoveries unveiling how chick embryos develop their limbs. He discovered the apical ectodermal ridge (AER), the zone of polarizing activity (ZPA), and the domains of interdigital cell death within the developing limb and determined their function through experimental analysis. These discoveries provided the basis for subsequent molecular understanding of how vertebrate limbs are induced, patterned, and differentiated. These mechanisms are strongly conserved among the vast diversity of tetrapod limbs suggesting that relatively minor changes and tweaks to the molecular cascades are responsible for the diversity observed in nature. Analysis of the pathway systems first identified by Saunders in the context of animals displaying limb reduction show how alterations in these pathways have resulted in multiple mechanisms of limb and digit loss. Other classes of modification to these same patterning systems are seen at the root of other, novel limb morphological alterations and elaborations.

Figure 1

Schematics of signaling cascades in general tetrapod limb development and alterations that result in digit loss. (A) Major signaling factors and their spatial relationships in the developing tetrapod limb. (B) Schematic of digit loss in Australian skink species showing Shh expression in red and Msx expression in blue of stage 31 and 32 autopods and the resulting adult hind foot skeletons. Adapted from (Shapiro et al., 2003) (C) Representative mammalian species and their respective autopod patterning. Silhouettes of the mouse, jerboa, horse, cow, and camel (left to right) and their relative phylogeny. Limb bud schematics showing Shh expression in red and Ptch1 expression in light blue. Graded blue depicts anterior extent of Shh signaling. Autopod schematics below depict Msx expression or apoptosis (cow). Developing digits are labeled one through five. Digits in red with asterisks are digits that get sculpted away by post-patterning apoptosis. Arrows in the autopods of the cow and the camel indicate angle of digit growth. Dotted lines indicate the weight-bearing axis of the limb for the respective animal.

Figure 2

Schematics depicting the alterations in the development of dolphin flippers, bat wings, and duck feet. (A) Dolphin flipper development from limb bud through Stage 9. Green depicts the AER and the graded black is the presumed influence of Fgf signaling. Developing digits are shown in white. Modified from (Richardson and Oelschläger, 2002). (B). Patterns of signaling molecules in animals with altered interdigital webbing. BMP and Msx expression is in blue, Gremlin expression in yellow, and Fgf8 expression in green.