The Role of Spatially Controlled Cell Proliferation in Limb Bud Morphogenesis

Abstract

Oriented cell behaviors likely have a more important role in limb bud elongation during development than previously suggested by the “growth-based morphogenesis” hypothesis.

Msx1 and Msx2 in limb mesenchyme modulate digit number and identity

“…However, contrary to apoptosis, which is restricted in time and space in the developing limb bud, proliferation is active in the whole limb bud at the stage of development we analyzed and lasts over several days, such that subtle changes, not detectable in our analysis, might be cumulative. It is highly plausible that proliferation plays a role in anterior polydactyly, but, to establish it, it would be necessary to conduct a systematic analysis of cell proliferation in three-dimensions at different stages of development, the kind of which is just starting to be accessible (Boehm et al, 2010;Gros et al, 2010;Wyngaarden et al, 2010).…”

Regulative patterning in limb bud transplants is induced by distalizing activity of apical ectodermal ridge signals on host limb cells

“…Despite its originality, this approach had a major disadvantage: it assumed uniform expansion along the P-D axis. It is now known that this is not the case, at least for the developing mouse limb (Boehm et al, 2010), while less clear evidence exists for the chicken limb (Hornbruch and Wolpert, 1970;Fernandez-Teran et al, 2006). The second problem is the limited ability to recognize which elements are formed from the graft and which from the host.…”

On “Growth and Form” and ASAPbio reform (Editorial)

“…Borkhvardt's hydromechanical theory was initially based on empirical observations on the growth of vertebrate limb buds (Borkhvardt, 2000) providing a convincing hypothesis of how interactions of the mesenchymal inner cell mass within the limb bud, its ectodermal sheath and the collagen fibers that link the opposite walls of the bud produce its final form. Although somewhat similar thoughts on a possible mechanical role of the ectoderm have been put forward in early reports on chick limb bud growth and morphogenesis (e.g., Hornbruch and Wolpert, 1970), they were not that clearly formulated and were not integrated to other biomechanical issues; hence, rejected (probably prematurely) by later experimenters (see Boehm et al, 2010 for discussion). The current work by Borkhvardt represents the fullest and the latest version of his theory of mechanical transformations of all living cavitary bodies and besides limb bud formation discusses issues as diverse as plant and animal cell outgrowths, endocytosis, cell division, gastrulation, amoeboid movement, and even muscle contraction, all considered from a single hydromechanical point of view.…”