Related Experiment Videos
Molecular cues for the development of adrenal chromaffin cells and their preganglionic innervation
A Schober1, K Krieglstein, K Unsicker
1Neuroanatomy, University of Heidelberg, Germany. andreas.schober@unz.uni-heidelberg.de
Abstract:
Based on recent evidence from in vitro and gene knockout/insertion studies, this short review summarizes the molecular scenario underlying the development of adrenal chromaffin cells and their preganglionic innervation. During migration of neural crest cells from the dorsal surface of the neural tube to their destinations in the sympathetic primordia and adrenal glands, precursors of the so-called sympathoadrenal (SA) cell lineage are exposed to signals from the notochord and ventral neural tube probably including the protein, Sonic hedgehog. These, and signals in the region of the dorsal aorta (members of the family of bone morphogentic proteins), where SA progenitor cells subsequently assemble, are essential for the induction of the adrenergic phenotype. SA progenitor cells subsequently differentiate into paravertebral and prevertebral sympathetic neurones, intra- and extra-adrenal chromaffin cells and intermediate SIF (small intensely fluorescent) cells. Based on in vitro studies with isolated SA and chromaffin progenitor cells, glucocortiocids have been claimed as essential for suppressing neuronal commitment and for channelling SA cells towards the chromaffin phenotype. However, mice deficient for a functional glucocorticoid receptor possess the full complement of adrenal chromaffin cells at birth, suggesting that signals other than glucocorticoid hormones may be important in triggering chromaffin cell differentiation. The cholinergic neurones that are preganglionic to adrenal chromaffin cells have their cell bodies located in the intermediolateral column (IML) of the spinal cord. For their normal development, these neurones require signals from the adrenal medulla, which include neurotrophin-4, a major neurotrophic factor of adrenal chromaffin cells. Taken together, these data provide a more complete picture of molecular signalling in the development of one of the most important neuroendocrine tissues in vertebrates.
Insights
Neural crest cells develop into adrenal chromaffin cells through molecular signals like Sonic hedgehog and bone morphogenetic proteins. Glucocorticoids are not essential for this critical neuroendocrine tissue development.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Adrenal chromaffin cells and their innervation are crucial neuroendocrine components.
- Neural crest cell migration and differentiation are complex developmental processes.
- Understanding the molecular signals governing sympathoadrenal lineage development is key.
Purpose of the Study:
- To review the molecular mechanisms underlying adrenal chromaffin cell development.
- To elucidate the role of various signaling molecules in sympathoadrenal cell differentiation.
- To examine the necessity of glucocorticoids and other factors in chromaffin cell fate determination.
Main Methods:
- Review of recent in vitro studies.
- Analysis of gene knockout/insertion studies in animal models.
- Integration of evidence on neural crest cell signaling pathways.
Main Results:
- Sympathoadrenal (SA) progenitor cells are influenced by notochord, ventral neural tube (Sonic hedgehog), and dorsal aorta (bone morphogenetic proteins) signals.
- SA progenitor cells differentiate into various neuronal and chromaffin cell types.
- Glucocorticoid receptor knockout mice exhibit normal adrenal chromaffin cell development, questioning the hormone's essential role.
Conclusions:
- Molecular signals, including Sonic hedgehog and bone morphogenetic proteins, are critical for adrenergic phenotype induction in SA cells.
- Alternative signaling pathways, not solely glucocorticoids, likely drive chromaffin cell differentiation.
- Development of preganglionic cholinergic neurons requires adrenal medulla-derived signals like neurotrophin-4.