Induction of a serotonergic and neuronal phenotype in thyroid C-cells

Abstract

We have investigated whether rat thyroid C-cells can acquire a phenotype similar to serotonergic neurons. C-cells are neural crest derived endocrine cells with some intrinsic neuronal and serotonergic properties. A relatively simple isolation scheme yielded cultures of about 50% initial purity, as measured by fluorescence activated cell sorting. These enriched C-cells could extend neurites up to 550 microns on a laminin-containing substratum in the presence of NGF. The cultured C-cells expressed neurofilaments and this expression was enhanced by NGF treatment. The C-cells also expressed two markers of the sympathoadrenal neural crest lineage, the mammalian achaete scute homolog-1 (MASH-1) transcription factor, and the B2 cell surface antigen. Interestingly, MASH-1 was not detectable after the C-cells were placed in culture, which is consistent with neuronal differentiation, since MASH-1 is only expressed in neuronal progenitors prior to differentiation. We then demonstrated that C-cells possess the fundamental features of serotonergic neurons: synthesis and secretion, uptake, and feedback control. The enriched C-cells, as well as the CA77 C-cell line, showed 5-HT immunostaining, expression of tryptophan hydroxylase mRNA, 5-HT1B autoreceptor mRNA, and 5-HT transporter mRNA and activity. NGF greatly induced 5-HT transporter activity as determined by sensitivity to sertraline, a selective 5-HT reuptake inhibitor. Based on these results, we propose that thyroid C-cells are derived from a vagal sympathoadrenal progenitor, similar to serotonergic enteric neurons, and can undergo neuronal transdifferentiation. Hence, these cells should provide suitable and convenient models for molecular and cellular studies on serotonergic neurons.

Binding of Upstream Stimulatory Factor and a Cell-specific Activator to the Calcitonin/Calcitonin Gene-related Peptide Enhancer

“…Interestingly, thyroid C cell lines and cultured C cells have a more neuronal phenotype that includes neurofilament expression, serotonergic properties, and CGRP production (7)(8)(9). This acquisition of neuronal properties is consistent with the common origin of C cells with serotonergic enteric neurons from a vagal sympathoadrenal progenitor in the neural crest (10). 2 Consequently, thyroid C cell lines can be used as a model to study the transcriptional regulation of CT/CGRP in both C cells and neurons.…”

Ca2+-Evoked Serotonin Secretion by Parafollicular Cells: Roles in Signal Transduction of Phosphatidylinositol 3′-kinase, and the γ and ζ Isoforms of Protein Kinase C

“…Eight isoforms of PKC, including each of the three main classes of PKC, conventional, novel, and atypical, were found to be expressed. The expression in PF cells of PKC␥, which was previously thought to be a brain-specific isoform (Nishizuka, 1995), may reflect the neural crest origin of PF cells and their relationship to neurons (Barasch et al, 1987a;Russo et al, 1992;Clark et al, 1995). The expression of many isoforms of PKC in a single cell is another characteristic that is reminiscent of neurons (Sacktor et al, 1993).…”

Calcium-sensing Receptor Modulates Cell Adhesion and Migration via Integrins

“…To address this gap, we investigated the signaling proteins and underlying mechanisms involved in CaSR-mediated cell adhesion and migration in rat medullary thyroid carcinoma cells (rMTC . These metastatic neuroendocrine cells, which endogenously express the CaSR, possess both neuronal and cancerous characteristics (18,19) and therefore have the potential to serve as a suitable model system to delineate CaSR protein-protein interactions involved in cell adhesion and/or migration.…”