Generation of pattern and form in the developing limb

Abstract

The developing limb is a major model for pattern formation in vertebrate embryos. Many of the seminal discoveries of the mechanisms involved in patterning have been made using chick embryos because of the ease of manipulating their developing limbs. More recently, the molecular basis of limb pattern formation has been increasingly uncovered and now, with the availability of genomic resources, the genetic approaches available are even more powerful. Nevertheless, since the limb is ultimately built of cells, gene action must ultimately be translated into cell behaviour and a major challenge will be to integrate genetics with molecular and cellular biology. In this review, we will first outline the stages in limb development, the major interacting signalling pathways that pattern the limb and the molecules involved. We will describe fate maps of the developing limb, and discuss what is known about cellular activities including proliferation, death, adhesiveness, communication and migration during the patterning process. Finally we will explore how these cell activities produce form.

Signalling Pathways in Development and Human Disease: A Drosophila Wing Perspective

“…Because these ligands act in a concentration-dependent manner at a distance from the cells expressing them, they can set adjacent domains of gene expression that partition the epithelium into different territories with specific gene expression patterns. This process is used reiteratively during the development of all multicellular organisms, and some examples are the patterning of segments in the embryonic epidermis and the subdivision of the imaginal discs into different territories in flies (Moussian and Roth, 2005), the generation of cell diversity in the vertebrate neural tube (Lupo et al, 2006), the establishment of the antero-posterior patterning in the vertebrate limbs and many others (Kumar, 2001;Duboc and Logan, 2009;Towers and Tickle, 2009;Arnold and Robertson, 2009). 5.…”

Zebrafish limb development is triggered by a retinoic acid signal during gastrulation

“…Limb buds are autonomous structures and limb growth and patterning is under the control of signals from within rather than from outside the buds (Tabin and Wolpert, 2007;Towers and Tickle, 2009). In contrast, determination of the territories where limb bud formation will occur, so called limb fields, depends on patterning processes that are less well understood (Capdevila and Izpisua Belmonte, 2001;Mercader, 2007;Allard and Tabin, 2009).…”

Spatiotemporal changes in cell adhesiveness during vertebrate limb morphogenesis

“…One of the main issues in limb development research is the understanding of how the undifferentiated mesenchymal cells of the limb bud form cartilaginous elements that have individual morphology (reviewed by Towers and Tickle, 2009b). As described in the Introduction section, the regulation of condensation is a significant step in limb morphogenesis.…”