Origination and innovation in the vertebrate limb skeleton: an epigenetic perspective

Abstract

The vertebrate limb has provided evolutionary and developmental biologists with grist for theory and experiment for at least a century. Its most salient features are its pattern of discrete skeletal elements, the general proximodistal increase in element number as development proceeds, and the individualization of size and shape of the elements in line with functional requirements. Despite increased knowledge of molecular changes during limb development, however, the mechanisms for origination and innovation of the vertebrate limb pattern are still uncertain. We suggest that the bauplan of the limb is based on an interplay of genetic and epigenetic processes; in particular, the self-organizing properties of precartilage mesenchymal tissue are proposed to provide the basis for its ability to generate regularly spaced nodules and rods of cartilage. We provide an experimentally based "core" set of cellular and molecular processes in limb mesenchyme that, under realistic conditions, exhibit the requisite self-organizing behavior for pattern origination. We describe simulations that show that under limb bud-like geometries the core mechanism gives rise to skeletons with authentic proximodistal spatiotemporal organization. Finally, we propose that evolution refines skeletal templates generated by this process by mobilizing accessory molecular and biomechanical regulatory processes to shape the developing limb and its individual elements. Morphological innovation may take place when such modulatory processes exceed a threshold defined by the dynamics of the skeletogenic system and elements are added or lost.

Shared rules of development predict patterns of evolution in vertebrate segmentation

“…Our results contribute to increasing evidence that activator-inhibitor interactions are involved in limb, digit and somite segmentation, and could reflect a universal design principle 4,[30][31][32][33][34][35] , but while confirmatory these results do not clarify the identity of the molecule(s) or the exact developmental mechanisms involved. We argue that the value of using the IC model is that, while previous models describe how segments form, they make no predictions about how they vary in size, and imply that elements are either independently formed or that segment proportions are largely the result of selection on later developmental events such as growth.…”

Life in the Slow Lane: The Effect of Reduced Mobility on Tadpole Limb Development

“…Hosseini and Hogg (1991) also reported that chick embryos paralyzed with a DMB solution have shorter tibia owing to the reduction of formation of perichondral bone and cartilage. Reduction in size of long bones seems to be correlated with a reduction of embryonic movement, which leads to a decrease in Type II collagen, aggrecan, and glycosaminoglycan expression, and the consequent reduction of cartilage-matrix synthesis (Newman and Mü ller, 2005). Because the cartilaginous precursors of the carpal and tarsal elements also are diminished in size, it is thought that the same processes affect long bones and elements of the manus and pes.…”

“…), all of which are the same in vertebrates. In fact, many of the factors involved in vertebrate limb outgrowth and shaping (e.g., Dlx, Lmx, Hox, R-fng, Fgf, Shh, and Wnt) originated in ancestral metazoans, in which they also controlled tissue outgrowth and shaping (Newman and Mü ller, 2005). However, differences in the reactivity of the mesenchymal tissue to produce joints, and the threshold levels to respond to mechanical stress in sesamoid could constitute interesting variations to these highly conservative response patterns.…”

Evolutionary Developmental Biology and the Limits of Philosophical Accounts of Mechanistic Explanation

“…In addition to a plethora of fossil studies and experimental investigations in extant species (e.g., chicken), the formation of the broadest aspects of the shape of different skeletal elements and their basic spatial position has been mathematically modeled using activator-inhibitor systems (Hentschel et al 2004;Newman et al 2008;Newman and Müller 2005). This basic skeletal pattern in the adult organism is a fairly qualitative phenomenon and its developmental explanation involves quantitative models.…”