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

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

doi:10.3390/ijms22136838

Cited by 6 publications

(5 citation statements)

References 76 publications

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“…For example, we find TNC expression to be specific to the vagal neural crest ( Figure 1C and D ), consistent with its requirement for migration into the hindgut by changing the extracellular microenvironment ( Akbareian et al, 2013 ). In addition, the sacral neural crest expresses high levels of SOX10-mediated Cdh19 ( Huang et al, 2022 ), as well as Pax3 and 5-HT3 for innervation and neuronal maturation in the pelvic ganglion ( Deal et al, 2021 ; Ritter et al, 2021 ). Ret is also known to be upregulated in vagal neural crest cells to mediate more invasive behavior than in sacral neural crest ( Delalande et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

Single-cell profiling coupled with lineage analysis reveals vagal and sacral neural crest contributions to the developing enteric nervous system

Jacobs-Li,

Tang,

et al. 2023

eLife

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During development, much of the enteric nervous system (ENS) arises from the vagal neural crest that emerges from the caudal hindbrain and colonizes the entire gastrointestinal tract. However, a second ENS contribution comes from the sacral neural crest that arises in the caudal neural tube and populates the post-umbilical gut. By coupling single cell transcriptomics with axial-level specific lineage tracing in avian embryos, we compared the contributions of embryonic vagal and sacral neural crest cells to the chick ENS and the associated peripheral ganglia (Nerve of Remak and pelvic plexuses). At embryonic day (E) 10, the two neural crest populations form overlapping subsets of neuronal and glia cell types. Surprisingly, the post-umbilical vagal neural crest much more closely resembles the sacral neural crest than the pre-umbilical vagal neural crest. However, some differences in cluster types were noted between vagal and sacral derived cells. Notably, RNA trajectory analysis suggests that the vagal neural crest maintains a neuronal/glial progenitor pool whereas this cluster is depleted in the E10 sacral neural crest which instead has numerous enteric glia. The present findings reveal sacral neural crest contributions to the hindgut and associated peripheral ganglia and highlight the potential influence of the local environment and/or developmental timing in differentiation of neural crest-derived cells in the developing ENS.

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Section: Discussionmentioning

confidence: 99%

Single-cell profiling coupled with lineage analysis reveals vagal and sacral neural crest contributions to the developing enteric nervous system

Jacobs-Li,

Tang,

et al. 2023

eLife

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“…The localization of the 5-HT 3 receptor at different organs has implications for signal pathways. For example, 5-HT 3 receptors in the colon induced colonic inflammation through substance P (SP) and the neurokinin-1 (NK1) receptor, and 5-HT 3 receptors signaling the neural crest (NC) alter the development of the visceral organs, including the lower urinary tract (LUT) [70,71]. At the cellular level, most studies show functional receptors at the plasma membrane, although one study indicated the presence of a functional 5-HT 3 receptor on mitochondria; however, the exact location was not pinpointed [36].…”

Section: Discussionmentioning

confidence: 99%

5-HT3 Receptors on Mitochondria Influence Mitochondrial Function

Rao

Turek

Ratcliffe

et al. 2023

IJMS

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The 5-hydroxytryptamine 3 (5-HT3) receptor belongs to the pentameric ligand-gated cation channel superfamily. Humans have five different 5-HT3 receptor subunits: A to E. The 5-HT3 receptors are located on the cell membrane, but a previous study suggested that mitochondria could also contain A subunits. In this article, we explored the distribution of 5-HT3 receptor subunits in intracellular and cell-free mitochondria. Organelle prediction software supported the localization of the A and E subunits on the inner membrane of the mitochondria. We transiently transfected HEK293T cells that do not natively express the 5-HT3 receptor with an epitope and fluorescent protein-tagged 5HT3A and 5HT3E subunits. Fluorescence microscopy and cell fractionation indicated that both subunits, A and E, localized to the mitochondria, while transmission electron microscopy revealed the location of the subunits on the mitochondrial inner membrane, where they could form heteromeric complexes. Cell-free mitochondria isolated from cell culture media colocalized with the fluorescent signal for A subunits. The presence of A and E subunits influenced changes in the membrane potential and mitochondrial oxygen consumption rates upon exposure to serotonin; this was inhibited by pre-treatment with ondansetron. Therefore, it is likely that the 5-HT3 receptors present on mitochondria directly impact mitochondrial function and that this may have therapeutic implications.

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“…For example, we find Tnc expression to be specific to the vagal neural crest (Fig 1C, D), consistent with its requirement for migration into the hindgut by changing the extracellular microenvironment 22 . In addition, the sacral neural crest expresses high levels of Sox10 -mediated Cdh19 23 , and well as Pax3 and 5-HT3 for innervation and neuronal maturation in the pelvic ganglion 24, 25 . Ret is also known to be upregulated in vagal neural crest cells to mediate more invasive behavior than in sacral neural crest 26 .…”

Section: Discussionmentioning

confidence: 99%

Single-cell profiling coupled with lineage analysis reveals distinct sacral neural crest contributions to the developing enteric nervous system

Tang

Jacobs-Li

et al. 2022

Preprint

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During development, the enteric nervous system (ENS) arises from neural crest cells that emerge from the neural tube, migrate to and along the gut, and colonize the entire intestinal tract. While much of the ENS arises from vagal neural crest cells that originate from the caudal hindbrain, there is a second contribution from the sacral neural crest that migrates from the caudal end of the spinal cord to populate the post-umbilical gut. By coupling single cell transcriptomics with axial-level specific lineage tracing in avian embryos, we compared the contributions between embryonic vagal and sacral neural crest cells to the ENS. The results show that the two neural crest populations form partially overlapping but also complementary subsets of neurons and glia in distinct ganglionic units. In particular, the sacral neural crest cells appear to be the major source of adrenergic/dopaminergic and serotonergic neurons, melanocytes and Schwann cells in the post-umbilical gut. In addition to neurons and glia, the results also reveal sacral neural crest contributions to connective tissue and mesenchymal cells of the gut. These findings highlight the specific properties of the sacral neural crest population in the hindgut and have potential implications for understanding development of the complex nervous system in the hindgut environment that may influence congenital neuropathies.

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

Cited by 6 publications

References 76 publications

Single-cell profiling coupled with lineage analysis reveals vagal and sacral neural crest contributions to the developing enteric nervous system

Single-cell profiling coupled with lineage analysis reveals vagal and sacral neural crest contributions to the developing enteric nervous system

5-HT3 Receptors on Mitochondria Influence Mitochondrial Function

Single-cell profiling coupled with lineage analysis reveals distinct sacral neural crest contributions to the developing enteric nervous system

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