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Neural Crest Stem Cells: from Development to Cancer

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Mol. Neurosci. | doi: 10.3389/fnmol.2019.00006

Schwann cell precursors generate the majority of chromaffin cells in Zuckerkandl organ and some sympathetic neurons in paraganglia

 Maria E. Kastriti1, 2,  Polina Kameneva1,  Dmitry Kamenev1,  Viacheslav Dyachuk1, 3, 4, Alessandro Furlan5, Marek Hampl6, 7, Fatima Memic1,  Ulrika Marklund1,  Francois Lallemend1,  Saida Hadjab1, Laura Calvo-Enrique1,  Kaj Fried1,  Patrik Ernfors1 and  Igor Adameyko1, 2*
  • 1Department of Physiology and Pharmacology, Karolinska Institute (KI), Sweden
  • 2Center for Brain Research, Medical University of Vienna, Austria
  • 3National Scientific Center of Marine Biology, Far East Branch (RAS), Russia
  • 4Department of Nanophotonics and Metamaterials, ITMO University, Russia
  • 5Cold Spring Harbor Laboratory, United States
  • 6Institute of Animal Physiology and Genetics (ASCR), Czechia
  • 7Department of Experimental Biology, Faculty of Science, Masaryk University, Czechia

In humans, neurosecretory chromaffin cells control a number of important bodily functions, including those related to stress response. Chromaffin cells appear as a distinct cell type at the beginning of midgestation and are the main cellular source of adrenalin and noradrenalin released into the blood stream. In mammals, two different chromaffin organs emerge at a close distance to each other, the adrenal gland and Zuckerkandl organ (ZO). These two structures are found in close proximity to the kidneys and dorsal aorta, in a region where paraganglioma, pheochromocytoma and neuroblastoma originate in the majority of clinical cases. Recent studies showed that the chromaffin cells comprising the adrenal medulla are largely derived from nerve-associated multipotent Schwann cell precursors (SCPs) arriving at the adrenal anlage with the preganglionic nerve fibers, whereas the migratory neural crest cells provide only minor contribution. However, the embryonic origin of the ZO, which differs from the adrenal medulla in a number of aspects, has not been studied in detail. The ZO is composed of chromaffin cells in direct contact with the dorsal aorta and the intraperitoneal cavity and disappears through an autophagy-mediated mechanism after birth. In contrast, the adrenal medulla remains throughout the entire life and furthermore, is covered by the adrenal cortex. Using a combination of lineage tracing strategies with nerve- and cell type-specific ablations, we reveal that the ZO is largely SCP-derived and forms in synchrony with progressively increasing innervation. Moreover, the ZO develops hand-in-hand with the adjacent sympathetic ganglia that coalesce around the dorsal aorta. Finally, we were able to provide evidence for a SCP-contribution to a small but significant proportion of sympathetic neurons of the posterior paraganglia. Thus, this cellular source complements the neural crest which acts as a main source of sympathetic neurons. Our discovery of a nerve-dependent origin of chromaffin cells and some sympathoblasts may help to understand the origin of pheochromocytoma, paraganglioma and neuroblastoma, all of which are currently thought to be derived from the neural crest or committed sympathoadrenal precursors.

Keywords: Zuckerkandl organ, extra-adrenal chromaffin cells, posterior trunk sympathetic ganglia, para-aortic sympathetic ganglia, Catecholamines, Schwann cell precursors

Received: 30 Oct 2018; Accepted: 09 Jan 2019.

Edited by:

Sabine Wislet, University of Liège, Belgium

Reviewed by:

Hiroshi Hibino, Niigata University, Japan
Christoph Wiegreffe, University of Ulm, Germany  

Copyright: © 2019 Kastriti, Kameneva, Kamenev, Dyachuk, Furlan, Hampl, Memic, Marklund, Lallemend, Hadjab, Calvo-Enrique, Fried, Ernfors and Adameyko. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Igor Adameyko, Karolinska Institute (KI), Department of Physiology and Pharmacology, Solna, Sweden, igor.adameyko@ki.se