title: Development of adrenal chromaffin cells is largely normal in mice lacking the receptor tyrosine kinase c-Ret.
abstract: c-Ret encodes a receptor tyrosine kinase that is essential for normal development of the kidney as well as enteric and sympathetic neurons. Since sympathetic neurons and neuroendocrine chromaffin cells originate from a common progenitor cell, we have examined the relevance of c-Ret for the development of adrenal chromaffin cells by analyzing mouse mutants lacking c-Ret. Adrenal chromaffin cells express c-Ret mRNA at embryonic day (E) 12.5 and 13.5, yet levels of expression decline at later embryonic and postnatal ages. Adrenal medullae of c-Ret deficient mice show normal numbers of tyrosine hydroxylase (TH)-immunoreactive cells at E13.5 and at birth. Ultrastructurally, adrenal chromaffin cells of c-Ret(-/-) mice appear unaltered: chromaffin cells develop typical secretory chromaffin granules, the morphological hallmark of chromaffin cells, and synaptic terminals appear normal. However, adrenaline levels and numbers of chromaffin cells immunoreactive for the adrenaline synthesizing enzyme phenylethanolamine-N-methyltransferase (PNMT) are reduced by about 30% in c-Ret-deficient mice arguing for a direct or indirect role of c-Ret in the regulation of PNMT. Thus, despite expression of c-Ret, adrenal chromaffin cells develop largely normal in mice lacking c-Ret. We therefore conclude that sympathetic neurons and neuroendocrine chromaffin cells profoundly differ in their requirement for c-Ret signaling during development.
authors.affiliation: Neuroanatomy and Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 307, D-69120 Heidelberg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Allmendinger
authors.forename: Elvira
authors.initials: E
authors.lastname: Stoeckel
authors.forename: Mart
authors.initials: M
authors.lastname: Saarma
authors.forename: Klaus
authors.initials: K
authors.lastname: Unsicker
authors.forename: Katrin
authors.initials: K
authors.lastname: Huber
mesh_terms: D000311:Adrenal Glands / Q000166:cytology* / Q000196:embryology / Q000254:growth & development* / Q000648:ultrastructure; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D019439:Chromaffin Cells / Q000502:physiology* / Q000648:ultrastructure; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D009638:Norepinephrine / Q000378:metabolism; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D015398:Signal Transduction; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; D014446:Tyrosine 3-Monooxygenase; D010625:Phenylethanolamine N-Methyltransferase; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C494999:Ret protein, mouse; D009638:Norepinephrine; D004837:Epinephrine