How Is the Vertebrae Limb Patterend?

0527680

How is the vertebrate limb patterned?

Abstract

The vertebrate limb has been and still is an important model for studying pattern formation in a developing embryo. Classical and contemporary experiments have identified key signalling centres within the developing limb as well as key signalling factors. These factors are involved in complex signalling cascades to pattern the limb causing sever phenotypic abnormalities if they fail.

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1. Introduction

The vertebrate limb provides an excellent model for studying pattern formation. The basic pattern is initially simple and in certain limbs can be easily manipulated surgically. The development of the vertebrate limb provides valuable information regarding intracellular signalling and cellular interactions (1).

The first morphological sign of limb development is a small protrusion of tissue from the lateral plate mesoderm (LPM) (1). In one of the earliest embryological studies, Harrison demonstrated that the limb forming region was able to give rise to fully developed limbs if transplanted to ectopic sites (2). This experiment was built upon, and in 1938 Hamburger demonstrated that limb type identity is determined by the origin of the graft (2). Now the main signalling molecules involved in limb development have been identified but much remains to be discovered.

The outgrowth and patterning of the limb depends on three signaling centers; the apical ectodermal ridge (AER), the polarizing region (ZPA) and the progress zone (PZ) (1). The vertebrate limb also develops along three primary axes; the antero-posterior (A-P), the dorso-ventral (D-V), and the proximo-distal (P-D) (1). The AER is found at the tip of the bud where the ectoderm is thickened. It runs along the D-V boundary and its main function is to pattern the P-D axis. Directly beneath it is the PZ which is composed of undifferentiated mescenchymal cells. Once the cells leave this zone they begin to differentiate. In the posterior margin of the limb bud the ZPA can found. This signalling centre is involved in patterning the A-P axis (1).

This essay will focus on the three axes of the vertebrate limb and how they establish limb identity. Embryological studies will be used to discuss the signalling molecules involved in limb patterning and how they all relate to each other with focus on the T box genes, the fibroblast growth factors, the Wnts and the sonic hedgehog gene.

2. T box genes control the identity of the fore and hind limbs

T box genes encode a group of transcription factors that are characterized by a highly

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