The Bhlh Protein Dimmed Controls Neuroendocrine Cell Differentiation In Drosophila

Neuroendocrine cells are specialized to produce, maintain and release large stores of secretory peptides. We show that the Drosophila dimmed/Mist1 bHLH gene confers such a pro-secretory phenotype on neuroendocrine cells. dimmed is expressed selectively in central and peripheral neuroendocrine cells. In dimmed mutants, these cells survive, and adopt normal cell fates and morphology. However, they display greatly diminished levels of secretory peptide mRNAs, and of diverse peptides and proteins destined for regulated secretion. Secretory peptide levels are lowered even in the presence of artificially high secretory peptide mRNA levels. In addition, overexpression of dimmed in a wild-type background produces a complimentary phenotype: an increase in secretory peptide levels by neuroendocrine cells, and an increase in the number of cells displaying a neuroendocrine phenotype. We propose that dimmed encodes an integral component of a novel mechanism by which diverse neuroendocrine lineages differentiate and maintain the pro-secretory state.