Twist 1 controls cell fate decisions within the cardiac neural crest

      During vertebrate development, a unique population of cells, termed neural crest cells, migrates throughout the developing embryo, generating various cell types, for example, the smooth muscle that divides the aorta and pulmonary artery where they connect to the heart, and the autonomic neurons, which coordinate organ function. The distinctions between neural crest cells that will form smooth muscle and those that will become neurons are thought to occur prior to migration. Here, we show that in mice with mutations of the transcription factor Twist1, a subpopulation of presumptive smooth muscle cells, following migration to the heart, instead mis-specify to resemble autonomic neurons. Twist1 represses transcription of the pro-neural factor Phox2b both through antagonism of its upstream effector, Sox10, and through direct binding to its promoter. Phox2b is absolutely required for autonomic neuron development, and indeed, the aberrant neurons in Twist1 mutants disappear when Phox2b is also mutated. Ectopic Twist1 expression within all neural crest cells disrupts the specification of normal autonomic neurons. Collectively, these data reveal that neural crest cells can alter their cell fate from mesoderm to ectoderm after they have migrated and that Twist1 functions to maintain neural crest cell potency during embryonic development.
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