title: Reduction of endogenous TGF-beta does not affect phenotypic development of sympathoadrenal progenitors into adrenal chromaffin cells.
abstract: Adrenal chromaffin cells and sympathetic neurons are related, but phenotypically distinct derivatives of the neural crest. Molecular cues that determine the chromaffin cell phenotype have not yet been identified; in contrast to a widely held belief, glucocorticoid signaling is apparently not relevant (Development 126 (1999) 2935). Transforming growth factor-betas (TGF-betas) regulate various aspects of embryonic development and are expressed in the environment of sympathoadrenal (SA) progenitor cells. We have previously shown that neutralization of endogenous TGF-beta from E4 to E8 in the quail embryo significantly increases numbers of adrenal tyrosine hydroxylase-positive cells. Whether endogenous TGF-beta may also be involved in influencing phenotypic development of adrenal chromaffin cells and their SA progenitors has not been analyzed. We now demonstrate that neutralization of endogenous TGF-beta1, -beta2 and -beta3 with a pan-anti-TGF-beta antibody in quail embryos during distinct time windows does not alter phenotypic development of chromaffin cells. In situ hybridizations revealed unaltered expression of neurofilament (NF-160), synaptotagmin I and neurexin I in adrenal glands. Likewise, the NF-associated antigen 3A10, and polyphosphorylated NF epitopes (RT 97) were unaltered. Most importantly, the typical ultrastructure of adrenal chromaffin cells including their large chromaffin secretory granules, a hallmark of the neuroendocrine phenotype, which distinguishes them from sympathetic neurons, was not affected. We therefore conclude that neutralization of endogenous TGF-beta influences chromaffin cell proliferation, but does not interfere with the development of the typical chromaffin cell phenotype.
authors.affiliation: Neuroanatomy and Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany.
authors.forename: S E
authors.initials: SE
authors.lastname: Combs
authors.forename: U
authors.initials: U
authors.lastname: Ernsberger
authors.forename: K
authors.initials: K
authors.lastname: Krieglstein
authors.forename: K
authors.initials: K
authors.lastname: Unsicker
mesh_terms: D000311:Adrenal Glands / Q000166:cytology* / Q000196:embryology*; D000818:Animals; D002135:Calcium-Binding Proteins; D019070:Cell Lineage; D019439:Chromaffin Cells / Q000166:cytology*; D018076:DNA, Complementary / Q000378:metabolism; D006023:Glycoproteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D009479:Neuropeptides; D010641:Phenotype; D011784:Quail; D013234:Stem Cells; D050863:Synaptotagmin I; D050857:Synaptotagmins; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050863:Synaptotagmin I; D016212:Transforming Growth Factor beta; C112162:neurexophilin; D050857:Synaptotagmins