5-HT3 Signaling Alters Development of Sacral Neural Crest Derivatives That Innervate the Lower Urinary Tract.
5-HT3 Signaling Alters Development of Sacral Neural Crest Derivatives That Innervate the Lower Urinary Tract.
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DOI：
10.3390/ijms22136838
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发表时间：
2021-06-25
影响因子：
5.6
通讯作者：
Southard-Smith EM
中科院分区：
文献类型：
--
作者：
Ritter KE;Buehler DP;Asher SB;Deal KK;Zhao S;Guo Y;Southard-Smith EM
自主神经系统起源于神经嵴（NC），并为内脏器官（包括下尿路（LUT））的平滑肌提供运动神经支配。在胎儿发育过程中，骶骨NC细胞定植于尿生殖窦，形成膀胱颈两侧的盆神经节（PG）。PG神经元的协调活动是正常排尿所必需的，然而，对PG神经元多样性的发展知之甚少。为了发现参与PG神经发生的候选基因，进行了骶骨NC和发育PG的转录组分析，并且我们鉴定了3型5-羟色胺受体（5-HT 3，由Htr 3a和Htr 3b编码）的富集。我们确定Htr 3a是在骶骨NC祖细胞中上调并在分化的PG神经元中维持的首批5-羟色胺受体基因之一。在体外培养表明，5-HT 3信号的中断改变骶骨NC细胞的分化结果，而5-HT 3的刺激，在胚胎盆神经节严重减少神经突乔木生长。总的来说，这项研究提供了一个宝贵的资源，PG发展的信号通路的分析，确定5-HT 3作为一种新的调节NC谱系多样化和周围神经系统中的神经元成熟，并表明，扰动5-HT 3信号在妊娠期有可能改变膀胱功能以后的生活。
The autonomic nervous system derives from the neural crest (NC) and supplies motor innervation to the smooth muscle of visceral organs, including the lower urinary tract (LUT). During fetal development, sacral NC cells colonize the urogenital sinus to form pelvic ganglia (PG) flanking the bladder neck. The coordinated activity of PG neurons is required for normal urination; however, little is known about the development of PG neuronal diversity. To discover candidate genes involved in PG neurogenesis, the transcriptome profiling of sacral NC and developing PG was performed, and we identified the enrichment of the type 3 serotonin receptor (5-HT3, encoded by Htr3a and Htr3b). We determined that Htr3a is one of the first serotonin receptor genes that is up-regulated in sacral NC progenitors and is maintained in differentiating PG neurons. In vitro cultures showed that the disruption of 5-HT3 signaling alters the differentiation outcomes of sacral NC cells, while the stimulation of 5-HT3 in explanted fetal pelvic ganglia severely diminished neurite arbor outgrowth. Overall, this study provides a valuable resource for the analysis of signaling pathways in PG development, identifies 5-HT3 as a novel regulator of NC lineage diversification and neuronal maturation in the peripheral nervous system, and indicates that the perturbation of 5-HT3 signaling in gestation has the potential to alter bladder function later in life.
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GUDMAP数据库 - 用于泌尿生殖器研究的在线资源。
DOI：
10.1242/dev.063594
发表时间：
2011-07
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Harding SD;Armit C;Armstrong J;Brennan J;Cheng Y;Haggarty B;Houghton D;Lloyd-MacGilp S;Pi X;Roochun Y;Sharghi M;Tindal C;McMahon AP;Gottesman B;Little MH;Georgas K;Aronow BJ;Potter SS;Brunskill EW;Southard-Smith EM;Mendelsohn C;Baldock RA;Davies JA;Davidson D
通讯作者：
Davidson D
影响因子：
2.9
作者：
Edwards, E;Hampton, E;Wang, RY
通讯作者：
Wang, RY
影响因子：
5.2
作者：
Heanue, Tiffany A.;Pachnis, Vassilis
通讯作者：
Pachnis, Vassilis
影响因子：
16.2
作者：
Demarque, Michael;Spitzer, Nicholas C.
通讯作者：
Spitzer, Nicholas C.
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP