Abstract
Microphthalmia-associated transcription factor (MITF) is a member of MYC superfamily, associated with melanocyte cells, as it was discovered in depigmented mice. However, over the last years it was found to be involved in many cellular signaling pathways, among which oncogenesis, osteoclast differentiation, and stress response. In mammals, Mitf gene mutations can cause diverse syndromes affecting pigmentation of eyes or skin, bone defects and melanomas. As MITF protein homologs were also found in some invertebrates, we have isolated and characterized the MITF cDNAs from the sea urchin Paracentrotus lividus, referred to as Pl-Mitf. The in silico study of the secondary and tertiary structure of Pl-Mitf protein showed high conserved regions mostly lying in the DNA binding domain. To understand the degree of evolutionary conservation of MITF, a phylogenetic analysis was performed comparing the Pl-Mitf deduced protein with proteins from different animal species. Moreover, the analysis of temporal and spatial expression pattern of Pl-Mitf mRNA showed that it was expressed from the onset of gastrulation of the sea urchin embryo to the pluteus larva, specifically in primary mesenchymes cells (PMCs), the sea urchin skeletogenic cells, and in the forming archenteron, the larval gut precursor. In silico protein–protein interactions analysis was used to understand the association of MITF with other proteins. Our results put in evidence the conservation of the MITF protein among vertebrates and invertebrates and may provide new perspectives on the pathways underlying sea urchin development, even if further functional analyses are needed.
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Acknowledgements
This research was supported by the Joint Research Project 2015–2017, as part of the Bilateral Agreement of Scientific and Technological Cooperation between the Consiglio Nazionale delle Ricerche of Italy (CNR) and the Russian Foundation for Basic Research (RFBR). We thank Mr Mauro Biondo and Alessandro Pensato for technical assistance.
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The conception and the design of the work was formulated by RR and FZ. Bioinformatics analyses were done by RR. The laboratory experiments were performed by RR, MC and FZ. The statistic analysis was carried out by MC. The analyses of experimental data and interpretation of data were done by RR, NL and FZ. The manuscript was written, validated and revised by RR, NL, MC and FZ.
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Database: Pl-mitf nucleotide sequence data are available in the EMBL databases under the Accession Number: MK229196.
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10709_2019_77_MOESM1_ESM.pdf
Supplementary material 1—Fig. S1 “Boxshade” alignment of MITF protein sequences, deduced by the Clustal O alignment showed in Fig. S2. Black box, high conserved amino acids; grey box, moderately conserved amino acids (PDF 200 kb)
10709_2019_77_MOESM2_ESM.pdf
Supplementary material 2—Fig. S2 Clustal O alignment of MITF protein sequences from different organisms. Amino acids are color-coded with the default setting of the Clustal program: in pink the basic ones, in red the hydrophobic/non polar ones, in blue the acidic ones and in green the hydrophilic ones. See online version for full color (PDF 232 kb)
10709_2019_77_MOESM3_ESM.mp4
Supplementary material 3—Fig. S3 Movie of the high score 3D simulation Pl-Mitf protein, by I-tasser program. In blue the N-terminal of the protein, and in red the C-terminal (MP4 2046 kb)
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Russo, R., Chiaramonte, M., Lampiasi, N. et al. MITF: an evolutionarily conserved transcription factor in the sea urchin Paracentrotus lividus. Genetica 147, 369–379 (2019). https://doi.org/10.1007/s10709-019-00077-z
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DOI: https://doi.org/10.1007/s10709-019-00077-z