Líf - og heilbrigðisvísindaráðstefna Háskóla Íslands 2023

Mitf regulates cell identity and activity in projection neurons of olfactory bulb

Fatich Mechmet, Alba Sabaté San José, Snævar Sigurðsson, Ingvi Gautsson, Eiríkur Steingrímsson, Pétur Henry Petersen

Microphthalmia-associated transcription factor (Mitf) is a master regulator in melanocytes and mast cells. It has a central role in the generation and function of these cell types. Mitf is also expressed in projection neurons (PNs), mitral and tufted (M/T), of olfactory bulb (OB), the center of the brain responsible for processing olfactory information in the central nervous system. Previous data suggest that MITF plays a role in homeostatic intrinsic plasticity in the OB through the regulation of key potassium channel subunits expression. However, its general role in neurons is unknown. Here, we focused on identifying putative MITF target genes in PNs of the OB and examined the function of Mitf with regards to neuronal activity through odor exposure experiments, RNA sequencing, RNA in situ hybridization (RNA-ISH) and bioinformatic tools. Genes positively affected by MITF are expected to have altered expression in Mitf mutant neurons. Therefore, genes with decreased expression in M/T neurons in the absence of Mitf were chosen for further analysis. These genes are formed of two groups: genes likely to be inhibitory to neuronal activity and genes expressed specifically in middle tufted (T1) neurons, a subclass of PNs. RNA-ISH confirmed the decreased expression of selected genes and the absence of T1 markers in Mitf mutant OBs. The results of odor experiments also showed that Mitf mutant mice do not respond correctly to activity. Our results suggest Mitf affects the development and function of PNs, as in other cell types, and that these changes lead to different activity response.


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