Neuronal properties of a thyroid C-cell line: partial repression by dexamethasone and retinoic acid

We have analyzed the effect of extracellular stimuli on the differentiation state of the CA77 thyroid C-cell line as a model to understand the control of neural crest cell differentiation. In contrast to the endocrine C-cell phenotype, we found that CA77 cells have a neuronal phenotype characterized by laminin-induced neurites, neuronal antigens, and calcitonin gene-related peptide (CGRP) mRNA expression. Treatment with dexamethasone and retinoic acid reversibly repressed some of these neuronal characteristics to induce features more characteristic of the parental C-cells. In the case of dexamethasone treatment, there was a partial retraction and thinning of neurites, an increased number of secretory vesicles in the cell bodies, and about a 10-fold decrease in DNA synthesis. Treatment with retinoic acid alone or in combination with dexamethasone caused decreased cell adhesion and an even more extensive retraction of the neurites. Dexamethasone also biased the steady state levels of the alternatively spliced transcripts from the calcitonin/CGRP gene to favor calcitonin relative to CGRP mRNA. While retinoic acid treatment decreased both calcitonin and CGRP mRNA levels, the combination of dexamethasone and retinoic acid still yielded the increase in calcitonin relative to CGRP mRNA. These results suggest that glucocorticoids and retinoic acid may contribute to a late and reversible differentiation of thyroid C-cells by partly repressing neuronal properties.