pax3

PAX3, or paired box gene 3, is a transcription factor belonging to the PAX family. It encodes a nuclear protein with a DNA-binding paired box domain and regulatory regions that activate or repress transcription. The gene has several transcript variants encoding multiple isoforms that show tissue-specific expression.

During embryogenesis, PAX3 is critical for the formation and migration of neural crest cells, the development of skeletal muscle precursors (myogenesis), and the formation of pigment cells (melanocytes). It is expressed in the somites, limb buds, and certain craniofacial structures. PAX3 function is often coordinated with other transcription factors such as SOX10 and MITF to drive lineage specification.

Clinical significance: Heterozygous mutations in PAX3 cause Waardenburg syndrome type I and III, characterized by sensorineural deafness and pigmentary abnormalities; type III includes limb abnormalities. In cancer, a chromosomal translocation yielding the PAX3-FOXO1 fusion gene (most commonly t(2;13)(q35;q14)) drives the alveolar rhabdomyosarcoma phenotype; PAX3-FOXO1 acts as an aberrant transcriptional activator promoting oncogenesis. PAX3 dysregulation has also been observed in other contexts and may influence tumor behavior.

Evolution and models: PAX3 is highly conserved among vertebrates; mouse and zebrafish PAX3 orthologs are used to study muscle and neural crest development. Research tools include PAX3 knockout mice and knockdown in model organisms.