REQUIREMENT OF THE MASH-1 TRANSCRIPTION FACTOR FOR NEUROENDOCRINE DIFFERENTIATION OF THYROID C-CELLS

Thyroid C cells are neural crest-derived neuroendocrine cells that can acquire features similar to serotonergic neurons, Based on developmen tal and phenotypic markers, we have previously proposed that C cells a nd serotonergic enteric neurons arise from a common sympathoadrenal pr ogenitor, In this report, we genetically examined this relationship us ing mice lacking the mammalian achaete-scute homologue 1 (MASH-1) tran scription factor, since MASH-1 has recently been shown to be required for differentiation of serotonergic enteric neurons, We found that MAS H-1 knockout mice have a greatly reduced number of C cells based on th e lack of calcitonin and serotonin immunoreactivity, In contrast, calc itonin and serotonin were still expressed in cultured mature C cells t hat no longer express MASH-1, demonstrating that MASH-1 is not directl y required for the expression of these two markers, Hence, MASH-1 is r equired to establish the C-cell phenotype and supports the model that C cells lie in the neuronal differentiation pathway of the sympathoadr enal neural crest. (C) 1998 John Wiley & Sons, Inc.