title: 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.
authors.affiliation: New York Medical College, Valhalla, New York 10595, USA. newman@nymc.edu
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Newman
authors.forename: Gerd B
authors.initials: GB
authors.lastname: Müller
mesh_terms: D000818:Animals; D005075:Biological Evolution; D001696:Biomechanical Phenomena; D019521:Body Patterning; D001846:Bone Development; D044127:Epigenesis, Genetic; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D014714:Vertebrates / Q000196:embryology*