The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes
| Autor: | Debra L. Silver, Karen E. Leeds, Emily E. Miller, Hun-Way Hwang, William J. Pavan |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
SOX10
Population Sox10 Mitosis Cell Count Haploinsufficiency Melanocyte Biology Article Cell Line 03 medical and health sciences Mice 0302 clinical medicine Melanoblast medicine Animals Melanoblast development education Molecular Biology In Situ Hybridization 030304 developmental biology Body Patterning Cell Proliferation Genetics Hypopigmentation 0303 health sciences education.field_of_study SOXE Transcription Factors Neural crest Gene Expression Regulation Developmental Nuclear Proteins Cell Biology Exons Embryo Mammalian Cell biology G2 Phase Cell Cycle Checkpoints Mice Inbred C57BL medicine.anatomical_structure Neural Crest Exon junction complex Melanocytes Magoh 030217 neurology & neurosurgery Gene Deletion Developmental Biology |
| Zdroj: | Developmental biology. 375(2) |
| ISSN: | 1095-564X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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