Abstract
BackgroundNeurons in sympathetic ganglia and neuroendocrine cells in the adrenal medulla share not only their embryonic origin from sympathoadrenal precursors in the neural crest but also a range of functional features. These include the capacity for noradrenaline biosynthesis, vesicular storage and regulated release. Yet the regulation of neuronal properties in early neuroendocrine differentiation is a matter of debate and the developmental expression of the vesicle fusion machinery, which includes components found in both neurons and neuroendocrine cells, is not resolved.ResultsAnalysis of synaptic protein and pan-neuronal marker mRNA expression during mouse development uncovers profound differences between sympathetic neurons and adrenal chromaffin cells, which result in qualitatively similar but quantitatively divergent transcript profiles. In sympathetic neurons embryonic upregulation of synaptic protein mRNA follows early and persistent induction of pan-neuronal marker transcripts. In adrenal chromaffin cells pan-neuronal marker expression occurs only transiently and synaptic protein messages remain at distinctly low levels throughout embryogenesis. Embryonic induction of synaptotagmin I (Syt1) in sympathetic ganglia and postnatal upregulation of synaptotagmin VII (Syt7) in adrenal medulla results in a cell type-specific difference in isoform prevalence. Dicer 1 inactivation in catecholaminergic cells reduces high neuronal synaptic protein mRNA levels but not their neuroendocrine low level expression. Pan-neuronal marker mRNAs are induced in chromaffin cells to yield a more neuron-like transcript pattern, while ultrastructure is not altered.ConclusionsOur study demonstrates that remarkably different gene regulatory programs govern the expression of synaptic proteins in the neuronal and neuroendocrine branch of the sympathoadrenal system. They result in overlapping but quantitatively divergent transcript profiles. Dicer 1-dependent regulation is required to establish high neuronal mRNA levels for synaptic proteins and to maintain repression of neurofilament messages in neuroendocrine cells.
Highlights
Neurons in sympathetic ganglia and neuroendocrine cells in the adrenal medulla share their embryonic origin from sympathoadrenal precursors in the neural crest and a range of functional features
Protein levels differ, as observed by immunohistochemistry in rat sympathetic neurons and adrenal neuroendocrine cells [35], and Synaptotagmin I (Syt1) mRNA levels in chromaffin cells are low compared to neuronal cells including the sparse neurons found in the adrenal medulla [36]
To analyze how this is reflected in the gene expression pattern, sympathetic ganglia and adrenal glands were analyzed by in situ hybridization (ISH) for several synaptic protein mRNAs in 3-week-old to 3-month-old mice
Summary
Neurons in sympathetic ganglia and neuroendocrine cells in the adrenal medulla share their embryonic origin from sympathoadrenal precursors in the neural crest and a range of functional features. These include the capacity for noradrenaline biosynthesis, vesicular storage and regulated release. Studies of rodent development shaped the idea that both sympathetic neurons and adrenal chromaffin cells originate from the same sympathoadrenal progenitor cell, which already displays some neuronal features such as low molecular weight neurofilament protein (NF-L) [4,5,6,7,8]. This pattern of sequential expression of mRNAs for pan-neuronal and synaptic proteins with different time courses of mRNA accumulation is shared by other peripheral and central neuron populations [15], and provokes the question as to the contribution of transcriptional and post-transcriptional regulation
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