PITX2

Paired-like homeodomain transcription factor 2 also known as pituitary homeobox 2 is a protein that in humans is encoded by the PITX2 gene.

Function

This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. This protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein is involved in the development of the eye, tooth and abdominal organs. This protein acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Three transcript variants encoding distinct isoforms have been identified for this gene.

Pitx2 is responsible for the establishment of the left-right axis, the asymmetrical development of the heart, lungs, and spleen, twisting of the gut and stomach, as well as the development of the eyes. Once activated Pitx2 will be locally expressed in the left lateral mesoderm, tubular heart, and early gut which leads to the asymmetrical development of organs and looping of the gut. When Pitx2 is deleted, the irregular morphogenesis of organs results on the left hand side. Pitx2 is left-laterally expressed controlling the morphology of the left visceral organs. Expression of Pitx2 is controlled by an intronic enhancer ASE and Nodal. It appears that while Nodal controls cranial expression of Pitx2, ASE controls left – right expression of Pitx2, which leads to the asymmetrical development of the left sided visceral organs, such as the spleen and liver. Collectively, Pitx2 first acts to prevent the apoptosis of the extraocular muscles followed by acting as the myogenic programmer of the extraocular muscle cells. There have also been studies showing different isoforms of the transcription factor: Pitx2a, Pitx2b, and Pitx2c, each with distinct and non-overlapping functions.