Mice and chick embryos serve as ideal test subjects in the analysis of developmental characteristics. Through in-vivo manipulation, signaling frameworks have been constructed to explain and describe the development of limbs (Tickle, 2004). The basis of all development relies on several generalized processes. Development begins with the separation of cell fields on the basis of function, as signaling pathways are introduced into each region. This causes a cascade of reactions, and ultimately the differentiation of cell types (Johnson and Tabin, 1997). The development of the limb itself is controlled by several interacting processes. Positional information and the identity of the limb features are regulated by the expression of sonic hedgehog, as well as a variety of BMP proteins. These factors function as concentration dependant morphogens, and result in variable responses based on the localized dosages (Tickle, 1999). The overall orientation of these appendages is regulate by a variety of transcriptional controls, and collectively maintained through hox gene expression (Tarchini and Duboule, 2006). Several similarities of these processes are conserved between vertebrate species, although the mechanisms responsible for signal interpretation result in the variability of morphologies observed (Tickle, 2004).
[...] Further experimentation has shown that sonic hedgehog acts in a concentration dependent manner, and is a fundamental requirement of digit formation (Tickle, 2000) Limb development is also regulated on a higher order of positioning and orientation. A system of gene interactions, collectively known as Hox genes; program for the level and position of each limb. This essentially generates the body plan of the organism, governing the position of each separate limb. These hox genes facilitate and regulate various transcription factors, and overall function to organize the morphology of the organism (Tarchini and Duboule, 2006). [...]
[...] The activity of sonic hedgehog is localized to the posterior margin of the limb bud, and collectively called the “zone of polarizing activity” (ZPA) (Johnson and Tabin, 1997). The ZPA model relies on the implications of a morphogen gradient, whereas separate signals are expressed as a result of varying concentrations. Those cells in proximity to the ZPA would receive higher morphogen concentrations, and therefore develop posterior characteristics. Conversely, those cells at a distance to the XPA would receive lower concentrations of morphogen, and therefore develop anterior characteristics (Johnson and Tabin, 1997). [...]
[...] These studies have revealed that several biochemical pathways are conserved throughout the vertebrate phylum, and more specifically, the systems involved in generating limbs (Tickle, 2000). Initial limb development research was conducted in the 1940's to obtain information pertaining to the chemicals/molecules responsible for generating these cells/tissue. Several model organisms have been utilized to describe and explain these interactions. The mouse and chick have proven to be exceptional study subjects, as embryonic manipulation is relatively simple (Tickle, 2000). These organisms have provided us with a detailed framework of limb development, and have since been defined as the product of three primary interactions. [...]
[...] In the early stages of limb development, the chick bud generates a specialized avascular rim beneath its ectodermal tissue, although this process is not conserved within the mouse embryo (Tickle, 2004). Several similar characteristics also exist between the model species. The positional orientation of sonic hedgehog is highly conserved, located within the posterior margin of the limb bud. Several grafting experiments have demonstrated the high level of similarity in these pathways. These experiments revealed that the posterior signal information from a mouse limb bud could be transplanted to induce the formation of digits in the anterior region of the chicken limb (Tickle, 2000). [...]
[...] These factors allow for the progressive development of subsequent limb features. Ectoderm signaling molecules control the formation of the dorsal/ventral axis. Several transplantation experiments have been performed to demonstrate this function, and reveal that these signals are produced along a gradient. Each pole provides specific information, and through these interactions, the limb bud is situated along a particular axis (Tickle, 2000). This is primarily regulated through a Wnt signaling pathway, and is highly conserved among many vertebrates. These Wnt signaling molecules (Wnt7a) are localized to the dorsal ectoderm, and influence the expression of Lmx1 and engrailed along the dorsal ventral axis (Church and West, 2002). [...]
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