Objective Intro Materials Procedure Results Discussion Lit. Cited Prep Sheet
		Introduction Pax-1 is a transcription factor that functions in the development of chondrocytes from somitic sclerotome cells (Gilbert, 2003). These chondrocytes later give rise to portions of the axial skeleton, including vertebrae and portions of the ribs (Smith and Tuan 1995). Pax-1 expression is induced by Sonic Hedgehog protein from the notochord and is expressed in the ventral portions, or sclerotomes, of the somites. Specifically, Pax-1 protein is thought to be a necessary ventral fate patterning molecule required for the proper formation of the vertebrae (Koseki 1993). Evidence shows that pax-1 null mutants in mice have little to no formation of the ventral portions of their vertebrae and vertebral discs (Wallin, 1994). Valproic acid first began to be used as an anticonvulsant drug to treat epilepsy in the late 1960’s. It has been shown to be a means of controlling seizures. However valproic acid is able to cross the placenta and has been linked to several human birth defects (Polifka, 2002), such as facial and skeletal malformations. Other vertebrates show similar birth defects. For example, rats treated with valproic acid produced embryos with fused ribs, missing vertebrae, and kinky tails (Vorhees, 1987). The teratogenic activity of valproic acid is thought to stem from its down-regulation of the pax-1 gene thereby leading to skeletal malformations (Lammer, 1987). Axial skeletal precursor cells are derived from the scelerotome portion of somites. These bones form by the process of endochondrial ossification and rely on a cartilage template for proper patterning. These cartilage templates are made by chondrocytes, which in turn are sclerotome cells that were induced to differentiate by Pax-1. Chicken embryos exposed to valproic acid showed significant somite disorganization and malformation that was spatially correlated to a decressed level of Pax-1 expression (Barnes, 1996). © Cebra-Thomas, 2001 Last Modified: 14 July 2014 [Lab Protocols | Students | Cebra-Thomas | Course | Links ]