Pax3, a member of the PAX family of transcription factors, is characterized by a conserved paired box motif. The Pax3 protein, with an N-terminal DNA binding domain and a C-terminal transcriptional activation domain, is crucial in the development of skeletal muscle, central nervous system, and neural crest derivatives. It regulates target genes related to cell proliferation, survival, differentiation, and motility in these lineages [1].

In Pax3 hypomorphs (mutants with reduced Pax3 function), expressing only 10% functional Pax3 protein, there are exacerbated neural tube, neural crest, and muscle defects. Ectopic and up-regulated expression of Pax7, a paralog of Pax3, is observed in Pax3-expressing lineages. Deletion of Pax7 in these hypomorphs leads to outflow tract defects and in utero lethality, indicating a compensatory role of Pax7 in Pax3-related functions during development [2]. Pax3 deficiency in mice also causes a decrease in cochlear melanocytes, suggesting its requirement for the development of neural crest cell-derived cochlear melanocytes, which may be related to congenital hearing loss in human Waardenburg syndrome [3]. In mouse neuroblastoma cell line Neuro-2a, overexpression of Pax3 inhibits cell viability, proliferation, affects the cell cycle, and shortens neurite outgrowth [4].

In conclusion, Pax3 is essential for multiple developmental processes such as myogenesis, neural tube and neural crest development, and the development of cochlear melanocytes. Studies using Pax3-related genetic models, like hypomorphs, have revealed its critical roles in these processes and provided insights into related human diseases like Waardenburg syndrome.