Determination of Neural Crest Cell Fate at Neural Tube vs. Target Organ Level

Abstract

The neural crest is a transient pool of multipotent progenitor cells that give rise to different cell types within the vertebrate embryo. Trunk neural crest cells emigrate from the dorsal neural tube. They differentiate into the sensory and autonomic neurons, Schwann cells, chromaffin cells of adrenal medulla, and melanocytes. The neural crest derived sympathetic neurons, chromaffin cells, and small intensely fluorescent cells have been proposed to share a common sympathoadrenal progenitor. NGF has been reported to be important for the differentiation of the neuronal lineage and glucocorticoids for the differentiation of the endocrine lineage. However, based on analyses of mice lacking the glucocorticoid receptor or the adrenal cortex, glucocorticoids have been found to be necessary for the survival of adrenal chromaffin cells but not for their differentiation. In situ hybridisation analysis of different neuronal and adrenal markers has revealed heterogeneity of sympathoadrenal cells before invading the adrenal medulla and sympathetic ganglia, respectively. These findings challenged the classical hypothesis of chromaffin cell differentiation and suggested that adrenomedullary cells and sympathetic neurons might have distinct progenitors. We attempted to elucidate whether the fate of the chromaffin cells and the sympathetic neurons is predetermined at the level of the neural tube. To prove our hypothesis, we performed a single neural crest cell electroporation technique in combination with immunohistological analysis. Our results from single cell electroporation experiments strongly supported the hypothesis that chromaffin cells and sympathetic neurons originate from a single progenitor cell at the level of the neural tube. However, we cannot exclude that few sympathetic neurons and chromaffin cells have distinct progenitors. In the second part of this study, we aimed to screen for expression patterns for Notch signalling members. Based on the fact that Notch signalling is involved in sympathetic ganglia development, we attempted to investigate the potential involvement of Notch signalling in the differentiation of sympathoadrenal precursors toward neuronal and neuroendocrine derivatives. In the last part of the thesis, we have investigated the differences in the vascular pattern of adrenal gland and sympathetic ganglia in developing avian embryos. The environmental signals of adrenal gland and sympathetic ganglia might provide factors that influence the sympathoadrenal differentiation.