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PAX3, a transcription factor and multifunctional regulatory protein, is normally expressed during embryonic development. In the nervous system, PAX3 is involved in neural tube closure, neural crest development, and peripheral neuron differentiation. In the present study, PAX3 was reported as a novel regulator of GFAP transcription, and the overexpression and suppression of PAX3 could inhibit and promote NSC differentiation, respectively. In muscle development, PAX3 ensures the survival of myogenic progenitor cells with Pax3-expressing progenitors giving rise to both skeletal and smooth muscle cells. PAX3 also has a well-established role in the development of melanocytes during embryogenesis, and has recently been characterized as a molecular switch in the mature melanocyte. Mutations in PAX3 can cause Waardenburg syndrome.