Related Experiment Videos
Reduction of endogenous TGF-beta does not affect phenotypic development of sympathoadrenal progenitors into adrenal
S E Combs1, U Ernsberger, K Krieglstein
1Neuroanatomy and Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany.
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.
Insights
Transforming growth factor-betas (TGF-betas) influence chromaffin cell proliferation but do not affect the development of the chromaffin cell phenotype in quail embryos. This study clarifies TGF-beta
Area of Science:
- Developmental biology
- Neuroscience
- Cell biology
Background:
- Adrenal chromaffin cells and sympathetic neurons originate from neural crest cells but are phenotypically distinct.
- Molecular signals determining chromaffin cell phenotype are largely unknown.
- Transforming growth factor-betas (TGF-betas) are implicated in embryonic development and are present around sympathoadrenal (SA) progenitor cells.
Purpose of the Study:
- To investigate the role of endogenous TGF-betas in the phenotypic development of adrenal chromaffin cells and their SA progenitors.
- To determine if TGF-beta signaling influences the differentiation of chromaffin cells from progenitor cells.
Main Methods:
- Neutralization of endogenous TGF-beta1, -beta2, and -beta3 using a pan-anti-TGF-beta antibody in quail embryos during specific developmental windows.
- Analysis of phenotypic development through in situ hybridization for neural markers (NF-160, synaptotagmin I, neurexin I) and specific epitopes (3A10, RT 97).
- Assessment of chromaffin cell ultrastructure, focusing on secretory granules.
Main Results:
- Neutralization of TGF-beta did not alter the phenotypic development of chromaffin cells.
- Expression of key neural and chromaffin cell markers remained unchanged.
- The characteristic ultrastructure of adrenal chromaffin cells, including secretory granules, was unaffected.
Conclusions:
- Endogenous TGF-beta signaling primarily influences chromaffin cell proliferation rather than their phenotypic differentiation.
- TGF-beta is not essential for establishing the distinct neuroendocrine phenotype of adrenal chromaffin cells.
- These findings refine our understanding of the molecular mechanisms governing sympathoadrenal lineage development.