Budding behaviors: Growth of the limb as a model of morphogenesis

Abstract

Questions regarding morphogenesis have played second fiddle to those pertaining to pattern formation among the limb development set for some time. A recent series of publications has reinvigorated the search for mechanisms by which the limb bud arises, elongates and acquires its peculiar shape. While there are stage-specific variations, the theme that resonates across these studies is that mesoderm and cartilage cells in the limb bud exhibit polarity that drives directional movement and oriented division. Noncanonical Wnt signalling is important for these cell behaviors at all stages of limb development. While the emerging morphogenetic mechanisms underlying limb bud outgrowth are partly analogous to those of other developing structures, insights from the limb have the potential to reveal intriguing new mechanisms by which three dimensional mesoderm changes shape. Developmental Dynamics 240:1054-1062,

A dynamic Shh expression pattern, regulated by SHH and BMP signaling, coordinates fusion of primordia in the amniote face

“…Studies on the limb have shown that non-directional growth alone is unable to explain the shape changes the limb bud experiences during development. Rather, polarized cell activities, such as cell movement in the mesenchyme, appear to comprise the emergent properties that generate shape (Boehm et al, 2010;Hopyan et al, 2011). Results from work in our laboratory indicate that polarized cellular behaviors associated with cell movement are associated with facial shape (Li et al, 2013).…”

Cell polarity

“…For example, in the growth plate, loss of oriented cell behaviors leads to loss of proliferative column structure and generates bones that are reduced in length and greater in width. 46,81 One simple model derived from these observations is that oriented cell behaviors provide a driving force for tissue elongation in the developing skeleton, 46,84 analogous to a model previously proposed for events in zebrafish gastrulation. 85 In the context of the limb, this model has only been empirically tested in the growth plate, a tissue in which precise measurements of elongation have been performed.…”

Topological Sound and Flocking on Curved Surfaces

“…For instance, propagating mechanical waves have been shown to mediate cooperative force transmission among epithelial cells in wound-healing assays [84]. In many biological processes, cell motion takes place on curved surfaces, as in cell renewal and repair in the highly folded intestine [85] and the shaping of the early limb bud in developing embryos [86]. The effect of curvature on the dynamics of epithelial cells is beginning to be explored in vitro by examining collective cell migration on cylindrical capillaries of varying radii [21].…”