ZPA Limb Development

The role of ZPA in limb development

Introduction:

When we take a walk, draw, kick a ball, or stretch our arms out to give someone a hug, we are using one of the remarkable products of nature’s biological processes – our limbs. We may take our arms and legs for granted, but the developmental steps that are required for these appendages of our bodies for form is nothing short of amazing. In looking at the human embryo, scanning electron micrographs show upper limb buds appearing on day 24 of embryonic development and lower limb buds appearing on day 28 as projections on either side of the lateral body wall (Larsen, 2015). These initial limb buds are formed from a core of mesodermal cells derived from the lateral plate mesoderm surrounded by

Much of this research has focused on the pattern formation that occurs in the limb along the antero-posterior axis in particular. In 1968, John Saunders and Mary Gasseling discovered a region of mesoderm on the posterior side of the limb bud known as the zone of polarizing activity (ZPA) (Saunders and Gasseling, 1968). When the posterior region of mesodermal cells was grafted to the anterior side of another chick limb bud, an amazing thing happened - a wing with a mirror-image pattern developed (Figure 3). The normal pattern of digits for a chick wing is 2-3-4 going anteriorly to posteriorly; the pattern of digits that developed in Saunders’ research was 2-3-4-4-3-2. How did this extraordinary result occur? There has been much research on the molecular and genetic mechanisms underlying ZPA’s role in limb development to answer this, leading to the ZPA becoming one of the best understood examples of an ‘organizer’ facilitating cell communications in vertebrate embryonic development (Tickle, 2002). It is the development of scientific understanding regarding these molecular and genetic mechanisms that will be the focus of this

The model proposed what Wolpert called a ‘polarity potential’ across the limb bud emanating from the ZPA; cells acquire their position in the limb bud as a result of a concentration gradient created by a morphogen produced in the polarizing region (Tickle, 2002). Cells surrounded by higher concentrations on the posterior side of the limb bud near the ZPA develop into posterior digits, whereas cells on the anterior side, farther away are surrounded by lower concentrations as the morphogen diffuses and form anterior digits. Research by Tickle et al. (1975) provided evidence for this model. Grafts from the ZPA were pinned at sequential locations along the antero-posterior axis of chick embryos (at different levels of somites). Digit formation appeared to follow a graded pattern in response to the grafts at various locations (Table 1). Contrary to this evidence for a concentration gradient signalling system, research conducted on cockroach legs, Drosophila imaginal dicks, and amphibian limbs was put forth that suggested