Oral communication, CS1 / C1

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Ets1 interacts with Sox10 during murine melanocyte development

SPEAKER A. Saldana-Caboverde #whois submiter ?
AUTHOR(s) A. Saldana-Caboverde, L. Kos

Melanocytes are derived from pluripotent neural crest (NC) cells, which arise from the dorsal aspect of the neural tube. Several genes required for the specification of melanocytes from the NC have been identified via the study of mouse pigmentation mutants. Recently, the deletion of the transcription factor Ets1 was shown to cause hypopigmentation in mice; however, the role of Ets1 in melanocyte development is unknown. Ets1 is a helix-turn-helix transcription factor that is expressed in various developing organs and tissues in the mouse embryo, including the NC. Our goal is to determine the temporal requirement and mechanism of action of Ets1 in melanocyte development. To this end, embryos from crosses between Ets1+/- and Dct-LacZ transgenic mice, in which LacZ expression is driven to melanoblasts under the control of the Dopachrome tautomerase (Dct) promoter, were harvested between embryonic days (E) 11.5-15.5 and LacZ staining was performed. Ets1-/- embryos have fewer melanoblasts compared to Ets1+/- and wild type littermates. Additionally, cell survival and proliferation assays suggest that the lack of Ets1 does not result in increased melanoblast cell death between E11.5-12.5 or in decreased melanoblast proliferation at E11.5. It is possible that Ets1 affects trunk NC cells prior to melanocytic fate specification at E10.5. To determine if this is the case, E9.5 embryos from crosses between Ets1+/- and Sox10+/LacZ mice, in which the LacZ gene was inserted in the Sox10 locus, are currently being harvested and the number and position of Sox10+ cells are being examined via LacZ staining. To further examine a putative relationship between Ets1 and Sox10, Ets1+/- mice were crossed to Sox10+/LacZ mice and the hypopigmentation phenotypes of the double heterozygous progeny were compared to that of the single heterozygotes. The incidence of ventral hypopigmentation in Ets1+/-::Sox10+/LacZ (n=17) mice was significantly higher than that of Ets1+/- (n=19) and Sox10+/LacZ (n=17) mice (p=0.001). Additionally, the area of hypopigmentation of Ets1+/-::Sox10+/LacZ mice was significantly greater than the sum of the areas of hypopigmentation of Ets1+/- and Sox10+/LacZ mice (p=0.006). Together, our results suggest that Ets1 is required for melanocyte development on or before E11.5 but does not appear to regulate melanoblast survival or proliferation at this age. Our results also indicate that Ets1 interacts synergistically with Sox10 during melanocyte development.



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