title: Differences in CART expression and cell cycle behavior discriminate sympathetic neuroblast from chromaffin cell lineages in mouse sympathoadrenal cells.
abstract: Adrenal medullary chromaffin cells and peripheral sympathetic neurons originate from a common sympathoadrenal (SA) progenitor cell. The timing and phenotypic changes that mark this lineage diversification are not fully understood. The present study investigated the expression patterns of phenotypic markers, and cell cycle dynamics, in the adrenal medulla and the neighboring suprarenal ganglion of embryonic mice. The noradrenergic marker, tyrosine hydroxylase (TH), was detected in both presumptive adrenal medulla and sympathetic ganglion cells, but with significantly stronger immunostaining in the former. There was intense cocaine and amphetamine-regulated transcript (CART) peptide immunostaining in most neuroblasts, whereas very few adrenal chromaffin cells showed detectable CART immunostaining. This phenotypic segregation appeared as early as E12.5, before anatomical segregation of the two cell types. Cell cycle dynamics were also examined. Initially, 88% of Sox10 positive (+) neural crest progenitors were proliferating at E10.5. Many SA progenitor cells withdrew from the cell cycle at E11.5 as they started to express TH. Whereas 70% of neuroblasts (TH+/CART+ cells) were back in the cell cycle at E12.5, only around 20% of chromaffin (CART negative) cells were in the cell cycle at E12.5 and subsequent days. Thus, chromaffin cell and neuroblast lineages showed differences in proliferative behavior from their earliest appearance. We conclude that the intensity of TH immunostaining and the expression of CART permit early discrimination of chromaffin cells and sympathetic neuroblasts, and that developing chromaffin cells exhibit significantly lower proliferative activity relative to sympathetic neuroblasts.
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Victoria, 3010, Australia.
authors.forename: Wing Hei
authors.initials: WH
authors.lastname: Chan
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Victoria, 3010, Australia.
authors.forename: David G
authors.initials: DG
authors.lastname: Gonsalvez
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Victoria, 3010, Australia.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Young
authors.affiliation: Division of Genetic Medicine, Department of Medicine, Vanderbilt University School of Medicine, 529 Light Hall, 2215 Garland Avenue, Nashville, Tennessee.
authors.forename: E Michelle
authors.initials: EM
authors.lastname: Southard-Smith
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Victoria, 3010, Australia.
authors.forename: Kylie N
authors.initials: KN
authors.lastname: Cane
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Victoria, 3010, Australia.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Anderson
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D019439:Chromaffin Cells / Q000166:cytology*; D005260:Female; D051379:Mice; D009432:Neural Crest / Q000166:cytology / Q000196:embryology; D058953:Neural Stem Cells / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D011247:Pregnancy; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors
keywords: adrenal chromaffin cells; cell cycle dynamic; cocaine and amphetamine-regulated transcript peptide; phenotypic lineage marker; sympathoadrenal cells