Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis-SC, Campus Universitário,Trindade, Florianópolis, SC, 88040-900, Brazil.
National Institute of Science and Technology for Regenerative Medicine, Av. Carlos Chagas Filho, n°373, Rio De Janeiro, RJ, CEP: 21941902, Brazil.
Cell Mol Neurobiol. 2020 Apr;40(3):383-393. doi: 10.1007/s10571-019-00738-9. Epub 2019 Sep 25.
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.
神经嵴细胞(NCCs)是起源于周围神经系统(PNS)和皮肤黑素细胞的多能祖细胞和干细胞群,其受到微环境因素的深远影响,其中包括碱性成纤维细胞生长因子 2(FGF2)。在这项工作中,我们进一步研究了这种生长因子在鹌鹑躯干 NCC 形态发生中的作用,并证明其通过刺激细胞增殖而主要对 NCC 生长具有巨大影响,但也减少了细胞死亡,尽管 NCC 从神经管外植体的迁移不受影响。此外,在 FGF2 处理后,观察到早期 NCC 标记物 Sox10 和 FoxD3 的表达减少和 HNK1 阳性 NCC 的增殖增加。由于这些标记物参与 NCC 胶质和黑素细胞命运的调节,因此研究了 FGF2 对 NCC 分化的影响。因此,在存在 FGF2 的情况下,记录到 Mitf 阳性的 NCC 以及 Mitf 和 BrdU 双重染色的 NCC 的比例增加。此外,用 FGF2 处理,然后用分化培养基处理,导致黑色素表达增加,黑色素着色的黑素细胞比例增加,而神经胶质标记 Schwann 髓鞘蛋白(SMP)没有改变。总之,这些数据进一步揭示了 FGF2 在 NCC 增殖、存活和分化中的重要作用,特别是在黑素细胞发育中。这是首次证明 FGF2 在 NCC 中的黑素细胞分化和 Mitf 阳性黑素母细胞的增殖中的作用。阐明胚胎 NCC 的分化过程使我们更接近于理解 PNS 的发育,然后着手寻找先进的技术来预防或治疗与 NCC 相关的疾病,也称为神经嵴病变。