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Development 129, 4729-4738 (2002)
Copyright © 2002 The Company of Biologists Limited

Development of chromaffin cells depends on MASH1 function

Katrin Huber1, Barbara Brühl1, François Guillemot2, Eric N. Olson3, Uwe Ernsberger1 and Klaus Unsicker1,*

1 Neuroanatomy, Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, INF 307, D-69120 Heidelberg, Germany
2 IGBMC,CNRS/INSERM/Université Louis Pasteur, BP 163, 67404 Illkirch Cédex, Cu de Strasbourg, France
3 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75239-9148, USA

*Author for correspondence (e-mail: klaus.unsicker{at}urz.uni-heidelberg.de)

Accepted 8 July 2002

The sympathoadrenal (SA) cell lineage is a derivative of the neural crest (NC), which gives rise to sympathetic neurons and neuroendocrine chromaffin cells. Signals that are important for specification of these two types of cells are largely unknown. MASH1 plays an important role for neuronal as well as catecholaminergic differentiation. Mash1 knockout mice display severe deficits in sympathetic ganglia, yet their adrenal medulla has been reported to be largely normal suggesting that MASH1 is essential for neuronal but not for neuroendocrine differentiation. We show now that MASH1 function is necessary for the development of the vast majority of chromaffin cells. Most adrenal medullary cells in Mash1–/– mice identified by Phox2b immunoreactivity, lack the catecholaminergic marker tyrosine hydroxylase. Mash1 mutant and wild-type mice have almost identical numbers of Phox2b-positive cells in their adrenal glands at embryonic day (E) 13.5; however, only one-third of the Phox2b-positive adrenal cell population seen in Mash1+/+ mice is maintained in Mash1–/– mice at birth. Similar to Phox2b, cells expressing Phox2a and Hand2 (dHand) clearly outnumber TH-positive cells. Most cells in the adrenal medulla of Mash1–/– mice do not contain chromaffin granules, display a very immature, neuroblast-like phenotype, and, unlike wild-type adrenal chromaffin cells, show prolonged expression of neurofilament and Ret comparable with that observed in wild-type sympathetic ganglia. However, few chromaffin cells in Mash1–/– mice become PNMT positive and downregulate neurofilament and Ret expression. Together, these findings suggest that the development of chomaffin cells does depend on MASH1 function not only for catecholaminergic differentiation but also for general chromaffin cell differentiation.

Key words: Sympathoadrenal cell lineage, Neuroendocrine cells, Chromaffin phenotype, Phox2b, Mouse







© The Company of Biologists Ltd 2002