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FGF2 Stimulates the Growth and Improves the Melanocytic Commitment of Trunk Neural Crest Cells

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Neural crest cells (NCCs) comprise a population of multipotent progenitors and stem cells at the origin of the peripheral nervous system (PNS) and melanocytes of skin, which are profoundly influenced by microenvironmental factors, among which is basic fibroblast growth factor 2 (FGF2). In this work, we further investigated the role of this growth factor in quail trunk NC morphogenesis and demonstrated its huge effect in NCC growth mainly by stimulating cell proliferation but also reducing cell death, despite that NCC migration from the neural tube explant was not affected. Moreover, following FGF2 treatment, reduced expression of the early NC markers Sox10 and FoxD3 and improved proliferation of HNK1-positive NCC were observed. Since these markers are involved in the regulation of glial and melanocytic fate of NC, the effect of FGF2 on NCC differentiation was investigated. Therefore, in the presence of FGF2, increased proportions of NCCs positives to the melanoblast marker Mitf as well as NCCs double stained to Mitf and BrdU were recorded. In addition, treatment with FGF2, followed by differentiation medium, resulted in increased expression of melanin and improved proportion of melanin-pigmented melanocytes without alteration in the glial marker Schwann myelin protein (SMP). Taken together, these data further reveal the important role of FGF2 in NCC proliferation, survival, and differentiation, particularly in melanocyte development. This is the first demonstration of FGF2 effects in melanocyte commitment of NC and in the proliferation of Mitf-positive melanoblasts. Elucidating the differentiation process of embryonic NCCs brings us a step closer to understanding the development of the PNS and then undertaking the search for advanced technologies to prevent, or treat, injuries caused by NC-related disorders, also known as neurocristopathies.

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This work was supported by the Ministério da Ciência, Tecnologia e Inovação/Conselho Nacional de Desenvolvimento Científico e Tecnológico (MCTI/CNPq/Brazil), Grants 465656/2014-5 and 309128/2013-7 from CNPq, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. Bianca L. Teixeira and Diego Amarante-Silva received a fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil). Diego Amarante-Silva also received a fellowship from the Programa de Doutorado Sanduíche no Exterior (PDSE/CAPES) processo BEX 6793-15-0 to develop part of his PhD in the Institut de la Vision—Paris-France. We would like to thank all the staff from the Multiuser Laboratory of Biology Studies (LAMEB/UFSC) for the technical support.

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BLT and DAS are both first authors. BLT, DAS, RCG, and AGT: Conceived and designed the experiments. DAS, BLT, and SBV: Performed experiments. BLT, DAS, and AGT: Analyzed data. BLT, DAS, and AGT: Wrote the manuscript.

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Correspondence to Andrea Gonçalves Trentin.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving animals were in accordance with the Animal Ethics Committee of Santa Catarina Federal University, Brazil (protocol number 6016021017).

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Teixeira, B.L., Amarante-Silva, D., Visoni, S.B. et al. FGF2 Stimulates the Growth and Improves the Melanocytic Commitment of Trunk Neural Crest Cells. Cell Mol Neurobiol 40, 383–393 (2020).

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