Neural crest cells are the primary innovation that led to evolution of the vertebrates, and transcription factors of the SoxE family (Sox8, Sox9 and Sox10) are among the central players regulating the development of these cells. In all vertebrates examined to date, one or more SoxE proteins are required for the formation of neural crest cells, the maintenance of their multipotency, and their survival. Later, SoxE proteins drive the formation of multiple neural crest derivatives including chondrocytes, melanocytes, and cells of the peripheral nervous system, particularly Schwann cells/peripheral glia. Given their multiple diverse roles in the development of the neural crest, it is important to understand how the activity of SoxE factors is controlled such that they direct the correct developmental outcome. While combinatorial control with other regulatory factors is clearly one mechanism for generating such functional versatility, modulation of SoxE activity, both by SoxD family factors and by post-translational modification, also appears to be important. Elucidating the mechanisms that control SoxE function is essential to understand the evolutionary origin of the vertebrates, as well as a host of SoxE-linked syndromes and diseases, and may prove crucial for developing stem cell based therapies that target SoxE-regulated cell types.
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