MITF regulates gene expression in middle tufted neurons and other projection neurons of the olfactory bulb

The microphthalmia-associated transcription factor (MITF) is a master transcription factor in melanocytes and plays equally important roles in mast cells. It is required for the generation, differentiation, and function of these cell types in vertebrates. Mitf is also expressed in the projection neurons of the olfactory bulb (OB), the mitral and tufted (M/T) cells. Loss of Mitf leads to neuronal hyperactivity in primary M/T cells but the general function of Mitf in neurons is unknown. Here, we identify putative MITF target genes in M/T cells, which show limited overlap with known targets in other cell types. These genes can be divided into two groups, those likely to inhibit neuronal activity and genes expressed specifically in a subclass of tufted cells, the middle tufted cells (mTCs). The mTCs are reduced in number in the Mitf mutant OB, suggesting a role for Mitf in the generation or survival of the mTCs and/or their function. Significance statementIdentifying MITF target genes in the OB offers insights into its role in olfaction and the regulation of neuronal activity as well as uncovering its role in mTCs. MITF may play a role in various other processes in neurons.