Oral communication, CS1 / C3

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

Does overexpression of the Strawberry Notch homolog 2 gene in Dopachrome tautomerase expressing cells trigger a defect in melanoblast specification ?

BACKGROUND AND OBJECTIVES: Strawberry Notch homolog 2 (Sbno2) is a mouse homolog of the sno gene, a regulator of the Notch pathway in Drosophila. Sbno2 was identified as a candidate gene for the patchwork (pwk) coat colour mutation. Mapped in the patchwork critical interval, Sbno2 was found overexpressed in the skin of patchwork embryos just before patchwork phenotype was first apparent. To test whether Sbno2 overexpression is sufficient for mimicking the patchwork phenotype, we produced mice overexpressing Sbno2 using the Dct promoter (Tg(Dct::Sbno2) mice). At birth, the transgenics have a white tail tip, belly spot and feet suggesting an alteration in melanocyte lineage development during embryogenesis. We attempted to determine the origin of the phenotype observed in newborn Tg(Dct::Sbno2) mice. METHODS: We studied the development of the melanocyte lineage in Tg(Dct::Sbno2) embryos between E10.5 and E18.5 using the Tg(Dct::lacZ) reporter gene, in toto X-Gal staining and immunohistochemistry. RESULTS: The density of melanoblasts was drastically reduced in Tg(Dct::Sbno2) embryos from E10.5 to E12.5. It increased gradually in the subsequent stages to become subnormal at E18.5. In addition, the Tg(Dct::lacZ) reporter gene was strongly expressed in several regions of Tg(Dct::Sbno2) embryos including the dorsal root ganglia (DRG) and spinal nerves all along the rostro-caudal axis from E10.5 onwards, cranial ganglia V and VII to XII from E10.5 to E12.5 and the cutaneous nerves from E12.5 to E18.5. Whether the number of nerves is increased in the transgenics is under investigation. Interestingly, the transgenics overexpressed Foxd3 in DRG and to a lesser extent, in the skin. The transcription factor FOXD3 is a marker of neural crest cells and Schwann cell precursors and is required for the maintenance of neural crest progenitors. FOXD3 controls the lineage choice between neural/glial and pigment cells by repressing Mitf in neural crest cells. Our current hypothesis is that, in Tg(Dct::Sbno2) embryos, overexpression of Sbno2 in DCT-positive cells may upregulate FOXD3 that in turn, would downregulate Mitf and suppress the melanoblast fate. The FOXD3-positive, MITF-negative cells would adopt a neural/glial fate while keeping on the Tg(Dct::lacZ) reporter gene. CONCLUSION: Our results suggest that in the mouse embryo overexpression of Sbno2 in DCT-positive cells leads to a cell-fate transition from the melanoblast to the neural/glial fate.

Advertisement from our sponsor: