Pax3 functions at a nodal point in melanocyte stem cell differentiation

Deborah Lang, Min Min Lu, Ll Huang, Kurt A. Engleka, Maozhen Zhang, Emily Y. Chu, Shari Lipner, Arthur I. Skoultchi, Sarah E. Millar, Jonathan A. Epstein

Research output: Contribution to journalArticle

268 Citations (Scopus)

Abstract

Most stem cells are not totipotent. Instead, they are partially committed but remain undifferentiated. Upon appropriate stimulation they are capable of regenerating mature cell types. Little is known about the genetic programmes that maintain the undifferentiated phenotype of lineage-restricted stem cells. Here we describe the molecular details of a nodal point in adult melanocyte stem cell differentiation in which Pax3 simultaneously functions to initiate a melanogenic cascade while acting downstream to prevent terminal differentiation. Pax3 activates expression of Mitf, a transcription factor critical for melanogenesis, while at the same time it competes with Mitf for occupancy of an enhancer required for expression of dopachrome tautomerase, an enzyme that functions in melanin synthesis. Pax3-expressing melanoblasts are thus committed but undifferentiated until Pax3-mediated repression is relieved by activated β-catenin. Thus, a stem cell transcription factor can both determine cell fate and simultaneously maintain an undifferentiated state, leaving a cell poised to differentiate in response to external stimuli.

Original languageEnglish (US)
Pages (from-to)884-887
Number of pages4
JournalNature
Volume433
Issue number7028
DOIs
StatePublished - Feb 24 2005

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Melanocytes
Cell Differentiation
Stem Cells
Totipotent Stem Cells
Transcription Factors
Catenins
Adult Stem Cells
Stem Cell Factor
Melanins
Phenotype
Enzymes

ASJC Scopus subject areas

  • General

Cite this

Lang, D., Lu, M. M., Huang, L., Engleka, K. A., Zhang, M., Chu, E. Y., ... Epstein, J. A. (2005). Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature, 433(7028), 884-887. https://doi.org/10.1038/nature03292

Pax3 functions at a nodal point in melanocyte stem cell differentiation. / Lang, Deborah; Lu, Min Min; Huang, Ll; Engleka, Kurt A.; Zhang, Maozhen; Chu, Emily Y.; Lipner, Shari; Skoultchi, Arthur I.; Millar, Sarah E.; Epstein, Jonathan A.

In: Nature, Vol. 433, No. 7028, 24.02.2005, p. 884-887.

Research output: Contribution to journalArticle

Lang, D, Lu, MM, Huang, L, Engleka, KA, Zhang, M, Chu, EY, Lipner, S, Skoultchi, AI, Millar, SE & Epstein, JA 2005, 'Pax3 functions at a nodal point in melanocyte stem cell differentiation', Nature, vol. 433, no. 7028, pp. 884-887. https://doi.org/10.1038/nature03292
Lang D, Lu MM, Huang L, Engleka KA, Zhang M, Chu EY et al. Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature. 2005 Feb 24;433(7028):884-887. https://doi.org/10.1038/nature03292
Lang, Deborah ; Lu, Min Min ; Huang, Ll ; Engleka, Kurt A. ; Zhang, Maozhen ; Chu, Emily Y. ; Lipner, Shari ; Skoultchi, Arthur I. ; Millar, Sarah E. ; Epstein, Jonathan A. / Pax3 functions at a nodal point in melanocyte stem cell differentiation. In: Nature. 2005 ; Vol. 433, No. 7028. pp. 884-887.
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