Journal of Neuroscience, Vol 7, 2874-2883, Copyright © 1987 by Society for Neuroscience
Induction of a neural phenotype in a serotonergic endocrine cell derived from the neural crest
JM Barasch, H Mackey, H Tamir, EA Nunez and MD Gershon
The thyroid parafollicular cell is an endocrine cell derived from the
neural crest that stores 5-hydroxytryptamine (5-HT). In common with
serotonergic neurons, but in contrast to 5-HT-storing cells that are not
neurectodermal derivatives, parafollicular cells also contain a specific
5-HT binding protein. Despite this similarity to serotonergic neurons,
parafollicular cells in situ were found to express an endocrine phenotype
with few neural characteristics. Thus, the cells costore 5-HT with
calcitonin, not calcitonin gene-related peptide (CGRP), which is the
product of the calcitonin gene expressed in neurons, and they do not
contain neurofilaments. The ability of adult parafollicular cells to
respond to microenvironmental perturbations by expressing neuronal
characteristics was examined. Sheep thyroid glands were dissociated, and
parafollicular cells were purified by affinity chromatography. The purified
parafollicular cells were grown in culture on a variety of substrates in
the presence or absence of the beta subunit of nerve growth factor
(beta-NGF). Parafollicular cells survived in culture for at least a week
but retained a roughly spherical shape. Nevertheless, a subset of the
cultured parafollicular cells began to display CGRP immunoreactivity. The
addition of beta-NGF to the cultured parafollicular cells induced a number
of them to extend neurites and increased the proportion of cells in which
CGRP immunoreactivity could be found. Neurite-bearing parafollicular cells
appeared not to survive for more than 2 d. While their survival was not
enhanced when they were grown on collagen, polylysine, laminin, or
reconstituted basal lamina, parafollicular cells that had extended neurites
in response to beta-NGF survived for at least a week when cocultured with
an explant of aneuronal chick hindgut. The effect of the gut was local and
only those neurite-bearing parafollicular cells that were growing in direct
contact with the explant survived. The thyroid parafollicular cell
therefore resembles another crest-derived endocrine cell, the adrenal
chromaffin cell, in being able to manifest neural properties in culture.
For the parafollicular cell these neural properties include the processing
of RNA encoded by the calcitonin gene to express CGRP and neurite outgrowth
in response to beta-NGF.