Oral Presentation 5th International Symposium on Phaeochromocytoma and Paraganglioma 2017

Stem cells and neural crest differentiation  (#4)

Quenten Schwarz 1 , Rachael Lumb 1 , Christiana Ruhrberg 2
  1. Centre for Cancer Biology, Adelaide, SA, Australia
  2. UCL Institute of Ophthalmology, University College London, London, United Kingdom

The adrenal gland is composed of a medulla and cortex that secrete adrenaline and corticosteroids into the systemic circulation to maintain physiological homeostasis and enable the autonomic stress response. Connections between central nervous system preganglionic sympathetic neurons and chromaffin cells in the adrenal medulla are essential for this stress response. However, the mechanisms that enable the formation of functional circuits between preganglionic neurons and chromaffin cells are currently unknown. By combining lineage tracing, gene expression studies and the analysis of engineered mouse mutants, we have found that axon innervation of the adrenal primordia precedes chromaffin cell differentiation, and that the neural crest cell precursors of chromaffin cells colonise the adrenal medulla in unison with axonal innervation. We further found that mice with axon guidance defects due to a lack of neuropilin  (NRP) 2 or its secreted ligand SEMA3F have defective innervation of the adrenal primordia and ectopically positioned chromaffin cells. Moreover, we found that SEMA3A cooperates with SEMA3F to guide preganglionic axons and chromaffin cell precursors into the adrenal primordia. These observations demonstrate that sympathoadrenal neural crest cells are guided to the adrenal primordia along the axons with which they will form functional connections to lay an anatomical foundation for the central regulation of the autonomic stress response.