NYMC Faculty Publications

The Vertebrate Limb: An Evolving Complex of Self-Organizing Systems

Journal Title

Progress in Biophysics & Molecular Biology

First Page

12

Last Page

24

Document Type

Article

Publication Date

September 2018

Department

Cell Biology and Anatomy

Abstract

The paired appendages (fins or limbs) of jawed vertebrates contain an endoskeleton consisting of nodules, bars and, in some groups, plates of cartilage, or bone arising from replacement of cartilaginous templates. The generation of the endoskeletal elements occurs by processes involving production and diffusion of morphogens, with, variously, positive and negative feedback circuits, adhesion, and receptor dynamics with similarities to the mechanism for chemical pattern formation proposed by Alan Turing. This review presents a unified interpretation of the evolution and functioning of these mechanisms. Studies are described indicating that protocondensations, compacted mesenchymal cell aggregates that prefigure the appendicular skeleton, arise through the adhesive activity of galectin-1, a matricellular protein with skeletogenic homologs in all jawed vertebrates. In the cartilaginous and lobe-finned fishes (and to a variable extent in ray-finned fishes) it additionally cooperates with an isoform of galectin-8 to constitute a self-organizing network capable of generating arrays of preskeletal nodules, bars and plates. Further, in the tetrapods, a putative galectin-8 control module was acquired that may have enabled proximodistal increase in the number of protocondensations. In parallel to this, other self-organizing networks emerged that acted, via Bmp, Wnt, Sox9 and Runx2, as well as transforming factor-beta and fibronectin, to convert protocondensations into skeletal tissues. The progressive appearance and integration of these skeletogenic networks over evolution occurred in the context of an independently evolved system of Hox protein and Shh gradients that interfaced with them to tune the spatial wavelengths and refine the identities of the resulting arrays of elements.

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