Microphthalmia‐associated transcription factor is expressed in projection neurons of the mouse olfactory bulb

Abstract

Microphthalmia‐associated transcription factor (Mitf) is a key regulator for differentiation of the neural crest‐derived melanocytes. Mitf consists of multiple isoforms, including melanocyte‐specific Mitf‐M and widely expressed Mitf‐A and Mitf‐H. Mitf mRNAs are also expressed in the brain, although the identity of Mitf‐expressing cells remains unknown. We therefore aimed to identify Mitf‐expressing cells in the brain. By the immunohistochemical analysis, we detected Mitf‐expressing cells only in the olfactory bulb of the C57BL/6 mouse. The Mitf‐expressing cells were then identified as projection neurons, mitral cells and tufted cells, both of which receive the signal from the olfactory neurons and transmit the information to the olfactory cortex. Real‐time RT‐PCR analysis showed the expression level of Mitf‐M mRNA was comparable to the expression levels of Mitf‐A and Mitf‐H mRNAs in the olfactory bulb. We then analyzed Mitf‐expressing neurons in the olfactory bulb of the homozygous black‐eyed white (Mitfmi‐bw) mouse that is characterized by the lack of melanocytes. Mitf was expressed in mitral cells and tufted cells in the olfactory bulb of the Mitfmi‐bw mouse, thereby excluding the contribution of melanocytes to the detected expression of Mitf‐M. In conclusion, Mitf, including Mitf‐M, is expressed in mitral cells and tufted cells of the olfactory bulb.

MITF and UV responses in skin: From pigmentation to addiction

“…Multiple MITF isoforms are known to be expressed from distinct promoters of the MITF gene, with different tissue expression profiles. Among those, the M‐isoform of MITF (MITF‐M) is expressed almost exclusively in melanocytes (Fuse, Yasumoto, Suzuki, Takahashi, & Shibahara, ), although it has also been detected in retinal pigment epithelium (Bharti, Liu, Csermely, Bertuzzi, & Arnheiter, ; Masuda & Esumi, ) and likely in mouse olfactory bulb projection neurons (mitral cells and tufted cells) (Ohba, Takeda, Yamamoto, & Shibahara, ). Besides CREB mentioned previously, multiple other transcription factors are involved in the regulation of MITF‐M at the transcriptional level, including paired box gene 3 (PAX3), SRY (sex‐determining region Y)‐box 10 (SOX10), lymphoid enhancer‐binding factor 1 (LEF1 or TCF), one cut domain 2 (ONECUT‐2), and MITF itself (reviewed in Kawakami & Fisher ).…”

Dysregulated Expression of MITF in Subsets of Hepatocellular Carcinoma and Cholangiocarcinoma

“…The antibody thus obtained recognizes a common region that is shared by multiple MITF isoforms, including MITF-M and widely expressed MITF-A and MITF-H (Fuse et al 1999). Importantly, this antibody has been successfully used in immunohistochemical analysis (Ohba et al 2015. Dilutions of primary antibodies were 1:400 for anti-MITF and 1:100 for anti-GLI1 (BIOSS, Woburn, MA, USA).…”

“…However, subsequent studies have suggested the pleiotropic functions of Mitf in various organs, including liver (Smith et al 1994), pancreas (Mazur et al 2013), kidney , lung (Takeda et al 2007), olfactory bulb (Ohba et al 2015), and frontal cortex (Takeda et al 2014;Ohba et al 2016). In particular, the Mitf vitiligo mouse, Mitf vit /Mitf vit , is characterized by retinal degeneration and the accumulation of retinyl palmitate in RPE and the liver (Smith et al 1994).…”

Mitf links neuronal activity and long-term homeostatic intrinsic plasticity

“…The transcription factor MITF, best known as a master regulator of melanocytes [18], is specifically expressed in the M/T neurons of the OB [19]. As the M/T neurons are the key output neurons in the OB circuitry, Mitf might play a role in olfaction [19].…”

“…The transcription factor MITF, best known as a master regulator of melanocytes [18], is specifically expressed in the M/T neurons of the OB [19]. As the M/T neurons are the key output neurons in the OB circuitry, Mitf might play a role in olfaction [19]. Mitf is also expressed in a subset of tufted cells, the external tufted cells (ETC), which are excitatory and synapse with MC, but do not project out of the OB [20][21][22].…”