Journal of Neuroscience, Vol 15, 6167-6178, Copyright © 1995 by Society for Neuroscience
Induction of a serotonergic and neuronal phenotype in thyroid C-cells
MS Clark, TM Lanigan, NM Page and AF Russo
Molecular Biology Program, University of Iowa, Iowa City 52242, USA.
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.
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