Reuter Isabel, Jäckels Jana, Kneitz Susanne, Kuper Jochen, Lesch Klaus-Peter, Lillesaar Christina
Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Germany.
Department of Physiological Chemistry, Biocenter, Am Hubland, University of Würzburg, Germany.
Biol Open. 2019 Jun 5;8(6):bio040683. doi: 10.1242/bio.040683.
In most vertebrates, including zebrafish, the hypothalamic serotonergic cerebrospinal fluid-contacting (CSF-c) cells constitute a prominent population. In contrast to the hindbrain serotonergic neurons, little is known about the development and function of these cells. Here, we identify fibroblast growth factor (Fgf)3 as the main Fgf ligand controlling the ontogeny of serotonergic CSF-c cells. We show that positively regulates the number of serotonergic CSF-c cells, as well as a subset of dopaminergic and neuroendocrine cells in the posterior hypothalamus via control of proliferation and cell survival. Further, expression of the ETS-domain transcription factor is downregulated after impairment. Previous findings identified as critical for the proliferation of serotonergic progenitors in the hypothalamus, and therefore we now suggest that Fgf3 acts via during early development to ultimately control the number of mature serotonergic CSF-c cells. Moreover, our analysis of the developing hypothalamic transcriptome shows that the expression of is upregulated upon loss-of-function suggesting activation of a self-compensatory mechanism. Together, these results highlight Fgf3 in a novel context as part of a signalling pathway of critical importance for hypothalamic development.
在大多数脊椎动物中，包括斑马鱼，下丘脑的血清素能脑脊液接触（CSF-c）细胞构成了一个显著的群体。与后脑血清素能神经元不同，关于这些细胞的发育和功能知之甚少。在这里，我们确定成纤维细胞生长因子（Fgf）3是控制血清素能CSF-c细胞个体发育的主要Fgf配体。我们表明，它通过控制增殖和细胞存活，正向调节血清素能CSF-c细胞的数量，以及下丘脑后部的一部分多巴胺能和神经内分泌细胞的数量。此外，ETS结构域转录因子的表达在Fgf3受损后下调。先前的研究发现该转录因子对下丘脑中血清素能祖细胞的增殖至关重要，因此我们现在认为Fgf3在早期发育过程中通过该转录因子起作用，最终控制成熟血清素能CSF-c细胞的数量。此外，我们对发育中的下丘脑转录组的分析表明，在Fgf3功能丧失时，该转录因子的表达上调，这表明激活了一种自我补偿机制。总之，这些结果突出了Fgf3在一个新的背景下，作为对下丘脑发育至关重要的信号通路的一部分。
