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Dev Biol. 2013 Mar 15;375(2):172-81. doi: 10.1016/j.ydbio.2013.01.004. Epub 2013 Jan 18.

The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes.

Author information

1
Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA. debra.silver@duke.edu

Abstract

Melanoblasts are a population of neural crest-derived cells that generate the pigment-producing cells of our body. Defective melanoblast development and function underlies many disorders including Waardenburg syndrome and melanoma. Understanding the genetic regulation of melanoblast development will help elucidate the etiology of these and other neurocristopathies. Here we demonstrate that Magoh, a component of the exon junction complex, is required for normal melanoblast development. Magoh haploinsufficient mice are hypopigmented and exhibit robust genetic interactions with the transcription factor, Sox10. These phenotypes are caused by a marked reduction in melanoblast number beginning at mid-embryogenesis. Strikingly, while Magoh haploinsufficiency severely reduces epidermal melanoblasts, it does not significantly affect the number of dermal melanoblasts. These data indicate Magoh impacts melanoblast development by disproportionately affecting expansion of epidermal melanoblast populations. We probed the cellular basis for melanoblast reduction and discovered that Magoh mutant melanoblasts do not undergo increased apoptosis, but instead are arrested in mitosis. Mitotic arrest is evident in both Magoh haploinsufficient embryos and in Magoh siRNA treated melanoma cell lines. Together our findings indicate that Magoh-regulated proliferation of melanoblasts in the dermis may be critical for production of epidermally-bound melanoblasts. Our results point to a central role for Magoh in melanocyte development.

PMID:
23333945
PMCID:
PMC3710740
DOI:
10.1016/j.ydbio.2013.01.004
[Indexed for MEDLINE]
Free PMC Article

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