Hypomorphic Sox10 alleles reveal novel protein functions and unravel developmental differences in glial lineages.
2007
The transcription factor Sox10 regulates early neural crest development,
specification of neural crest-derived lineages and terminal differentiation of
oligodendrocytes in the central nervous system. Here, we generated two novel
hypomorphic Sox10 alleles in the mouse. Mutant mice either expressed
a Sox10 protein with a triple alanine substitution in the dimerization domain,
or a Sox10 protein with a deletion in the central portion that we define as a
cell-specific transactivation domain. Phenotypic analysis revealed important
roles for a functional dimerization domain and the newly defined novel
transactivation domain in melanocyte and enteric nervous system development,
whereas early neural crest development and oligodendrocyte differentiation
were surprisingly little disturbed in both mutants. Unique requirements were
additionally detected for the novel transactivation domain in satellite glia
differentiation and during Schwann cell myelination, whereas DNA-dependent
dimerization was needed for immature Schwann cells to enter the promyelinating
stage. These two hypomorphic alleles thus uncover novel functions of Sox10 in
satellite glia and Schwann cells during late developmental stages and reveal
important developmental differences between these two types of peripheral glia
and oligodendrocytes regarding their reliance on Sox10.
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