5-HT3 Signaling Alters Development of Sacral Neural Crest Derivatives That Innervate the Lower Urinary Tract

Ritter, K. Elaine; Buehler, Dennis P.; Asher, Stephanie B.; Deal, Karen K.; Zhao, Shilin; Guo, Yan; Southard-Smith, E Michelle

doi:10.3390/ijms22136838

Open AccessArticle

5-HT3 Signaling Alters Development of Sacral Neural Crest Derivatives That Innervate the Lower Urinary Tract

by

K. Elaine Ritter

^1,†,

Dennis P. Buehler

^1,‡

,

Stephanie B. Asher

^1,§,

Karen K. Deal

¹,

Shilin Zhao

²,

Yan Guo

²

and

E Michelle Southard-Smith

^1,*

¹

Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA

²

Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA

^*

Author to whom correspondence should be addressed.

^†

Present affiliation: Division of Genetics, Metabolism & Genomic Medicine, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

^‡

Present address: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

^§

Present address: Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA.

Int. J. Mol. Sci. 2021, 22(13), 6838; https://doi.org/10.3390/ijms22136838

Submission received: 1 June 2021 / Revised: 19 June 2021 / Accepted: 22 June 2021 / Published: 25 June 2021

(This article belongs to the Special Issue Neural Crest Development in Health and Disease)

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Abstract

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.

Keywords: pelvic ganglia; bladder; autonomic nervous system; serotonin; Sox10; Htr3a

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MDPI and ACS Style

Ritter, K.E.; Buehler, D.P.; Asher, S.B.; Deal, K.K.; Zhao, S.; Guo, Y.; Southard-Smith, E.M. 5-HT3 Signaling Alters Development of Sacral Neural Crest Derivatives That Innervate the Lower Urinary Tract. Int. J. Mol. Sci. 2021, 22, 6838. https://doi.org/10.3390/ijms22136838

AMA Style

Ritter KE, Buehler DP, Asher SB, Deal KK, Zhao S, Guo Y, Southard-Smith EM. 5-HT3 Signaling Alters Development of Sacral Neural Crest Derivatives That Innervate the Lower Urinary Tract. International Journal of Molecular Sciences. 2021; 22(13):6838. https://doi.org/10.3390/ijms22136838

Chicago/Turabian Style

Ritter, K. Elaine, Dennis P. Buehler, Stephanie B. Asher, Karen K. Deal, Shilin Zhao, Yan Guo, and E Michelle Southard-Smith. 2021. "5-HT3 Signaling Alters Development of Sacral Neural Crest Derivatives That Innervate the Lower Urinary Tract" International Journal of Molecular Sciences 22, no. 13: 6838. https://doi.org/10.3390/ijms22136838

APA Style

Ritter, K. E., Buehler, D. P., Asher, S. B., Deal, K. K., Zhao, S., Guo, Y., & Southard-Smith, E. M. (2021). 5-HT3 Signaling Alters Development of Sacral Neural Crest Derivatives That Innervate the Lower Urinary Tract. International Journal of Molecular Sciences, 22(13), 6838. https://doi.org/10.3390/ijms22136838

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5-HT3 Signaling Alters Development of Sacral Neural Crest Derivatives That Innervate the Lower Urinary Tract

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