Mitf, with Yki and STRIPAK-PP2A, is a key determinant of form and fate in the progenitor epithelium of the Drosophila eye.

Autor: Zhang T; Department of Neuroscience & Physiology, Upstate Medical University, 505 Irving Avenue, NRB 4601, Syracuse, NY 13210, USA., Zhou Q; Department of Neuroscience & Physiology, Upstate Medical University, 505 Irving Avenue, NRB 4601, Syracuse, NY 13210, USA., Jusić N; Department of Neuroscience & Physiology, Upstate Medical University, 505 Irving Avenue, NRB 4601, Syracuse, NY 13210, USA., Lu W; Department of Neuroscience & Physiology, Upstate Medical University, 505 Irving Avenue, NRB 4601, Syracuse, NY 13210, USA., Pignoni F; Department of Neuroscience & Physiology, Upstate Medical University, 505 Irving Avenue, NRB 4601, Syracuse, NY 13210, USA; Department of Ophthalmology and Visual Sciences; Department of Biochemistry and Molecular Biology; Department of Cell and Developmental Biology, USA. Electronic address: pignonif@upstate.edu., Neal SJ; Department of Neuroscience & Physiology, Upstate Medical University, 505 Irving Avenue, NRB 4601, Syracuse, NY 13210, USA. Electronic address: neals@upstate.edu.
Jazyk: angličtina
Zdroj: European journal of cell biology [Eur J Cell Biol] 2024 Jun; Vol. 103 (2), pp. 151421. Date of Electronic Publication: 2024 May 15.
DOI: 10.1016/j.ejcb.2024.151421
Abstrakt: The Microphthalmia-associated Transcription Factor (MITF) governs numerous cellular and developmental processes. In mice, it promotes specification and differentiation of the retinal pigmented epithelium (RPE), and in humans, some mutations in MITF induce congenital eye malformations. Herein, we explore the function and regulation of Mitf in Drosophila eye development and uncover two roles. We find that knockdown of Mitf results in retinal displacement (RDis), a phenotype associated with abnormal eye formation. Mitf functions in the peripodial epithelium (PE), a retinal support tissue akin to the RPE, to suppress RDis, via the Hippo pathway effector Yorkie (Yki). Yki physically interacts with Mitf and can modify its transcriptional activity in vitro. Severe loss of Mitf, instead, results in the de-repression of retinogenesis in the PE, precluding its development. This activity of Mitf requires the protein phosphatase 2 A holoenzyme STRIPAK-PP2A, but not Yki; Mitf transcriptional activity is potentiated by STRIPAK-PP2A in vitro and in vivo. Knockdown of STRIPAK-PP2A results in cytoplasmic retention of Mitf in vivo and in its decreased stability in vitro, highlighting two potential mechanisms for the control of Mitf function by STRIPAK-PP2A. Thus, Mitf functions in a context-dependent manner as a key determinant of form and fate in the Drosophila eye progenitor epithelium.
Competing Interests: Declaration of Competing Interest The authors declare no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze: MEDLINE
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