Disease relevance of MITF

• Mitf overexpression caused hyperpigmentation in cultured rPECs and suppressed the changes in gene expression induced by bFGF [1].

High impact information on MITF

• Replacement of the extraocular mesenchyme with cranial mesenchyme, but not lateral plate mesoderm, could rescue expression of the RPE-marker Mitf [2].
• These findings showed that downregulation of Mitf expression is essential for the transdifferentiation of rPEC [1].
• Role of Mitf in differentiation and transdifferentiation of chicken pigmented epithelial cell [1].
• In embryos at stages later than stage 29 the signals for Mitf in the future iris, ciliary body, and posterior retinal regions become faint [1].
• Northern blotting showed that chicken Mitf is predominantly expressed in embryonic retinal pigmented epithelium (PE), but is expressed at low levels in other tissues [1].

Biological context of MITF

• Furthermore, we show that ectopic Mitf expression is able to protect the RPE from FGF2 induced transdifferentiation by inhibiting Pax6 upregulation [3].
• We observed that during the induction of transdifferentiation, downregulation of Mitf was not sufficient to induce transdifferentiation at E4 and that FGF2 was required to drive Pax6 protein expression and cell proliferation, both of which are necessary for transdifferentiation [3].
• Furthermore, overexpression of chicken Mitf via retroviral transfection into B/B homozygote bone marrow cells in cultures increased the number of TRAP-positive cells 2-3 fold more than that in control [4].
• Transfection of Mitf siRNA reduced Mitf synthesis at the mRNA and protein levels as analysed by real-time RT-PCR and Western blot [5].
• These data suggest siRNA can be an effective gene silencing approach in RPE, and reduction of Mitf expression is essential for the dedifferentiation of RPE cells [5].

Anatomical context of MITF

• Mitf encodes a basic helix-loop-helix-leucine-zipper (bHLHzip) protein that is known to function in the development of melanocytes, pigmented epithelial cells (PECs), osteoclasts, and mast cells [1].
• PURPOSE: To elucidate the early cellular events that take place during induction of retina regeneration in the embryonic chick, focusing on the relationship between fibroblast growth factor (FGF) signaling and the regulation of Pax6 and Mitf [3].
• Retina regeneration in the chick embryo is not induced by spontaneous Mitf downregulation but requires FGF/FGFR/MEK/Erk dependent upregulation of Pax6 [3].
• Suppression of Mitf by small interfering RNA induces dedifferentiation of chick embryonic retinal pigment epithelium [5].

Associations of MITF with chemical compounds

• Immunohistochemistry was used to examine pErk, Pax6, Mitf, and melanosomal matrix protein 115 (MMP115) immunoreactivity and bromodeoxyuridine (BrdU) incorporation at different time points after removing the retina [3].

Regulatory relationships of MITF

• In addition, we show that Mitf is spontaneously downregulated after removal of the retina even in the absence of FGF2 [3].
• Ectopic Mitf expression was able to inhibit transdifferentiation by acting downstream of FGFR/MEK/Erk signaling, likely by inhibiting the increase in Pax6 protein in the RPE [3].

References