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GDNF family receptors in the embryonic and postnatal rat heart and reduced cholinergic innervation in mice hearts lacking Ret or GFRα2
Author(s) -
Hiltunen Jukka O.,
Laurikainen Antti,
Airaksinen Matti S.,
Saarma Mart
Publication year - 2000
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/1097-0177(2000)9999:9999<::aid-dvdy1031>3.0.co;2-p
Subject(s) - biology , cholinergic , glial cell line derived neurotrophic factor , endocrinology , medicine , mesenchyme , receptor , neurturin , myotome , anatomy , microbiology and biotechnology , embryo , embryogenesis , neurotrophic factors , biochemistry , somite
Members of the GDNF family, which are important during peripheral nervous system development and kidney organogenesis, signal via Ret and GFRα receptors. Here we have studied their possible role in heart development. Gfra 1 was expressed in the endocardial cushion mesenchyme at E12 and later, in the developing and mature valves, and in the walls of the aorta and the pulmonary trunk. Gfra 2 was expressed in the outer layers of the aorta and pulmonary trunk and in the valves at E18–P60. Endocardial cells showed moderate Gfra 2 mRNA and protein expression between E12 and E15. Gfra 3 mRNA was detected, mainly postnatally, in scattered cells of the atria and the great vessels. In embryonic and postnatal rat cardiac ganglia, Ret and Gfra 2 transcripts were seen in the neurons, whereas Gfra 1 and Gfra 3 mRNA were preferentially found in non‐neuronal cells within the ganglia. GFRα2 immunoreactivity was seen in both cardiac ganglion neurons and their nerve fibers. There were no obvious non‐neuronal defects in hearts of Ret‐, GFRα1‐, or GFRα2‐deficient mice, suggesting that these receptors are not essential for gross cardiac development. However, E18 Ret‐deficient mice exhibited a reduced volume of cardiac ganglia and cholinergic innervation of the ventricular conduction system. Moreover, adult Gfra 2 −/− mice showed reduced cholinergic innervation by 40% in their ventricles and by 60% in the ventricular conduction system. These findings indicate that GFRα2/Ret signaling is required for normal cholinergic innervation of heart. © 2000 Wiley‐Liss, Inc.