Antibody markers identify a common progenitor to sympathetic neurons and chromaffin cells in vivo and reveal the timing of commitment to neuronal differentiation in the sympathoadrenal lineage

Abstract

Using specific antibody markers and double-label immunofluorescence microscopy, we have followed the fate of progenitor cells in the sympathoadrenal (SA) sublineage of the neural crest in developing rat embryos. Such progenitors are first recognizable in the primordial sympathetic ganglia at embryonic day 11.5 (E11.5), when they express tyrosine hydroxylase. At this stage, the progenitors also coexpress neuronal markers such as SCG 10 and neurofilament, together with a series of chromaffin cell markers called SA 1-5 (Carnhan and Patterson, 1991 a). The observation of such doubly labeled cells is consistent with the hypothesis that these cells represent a common progenitor to sympathetic neurons and adrenal chromaffin cells. Subsequent to E 11.5, expression of the chromaffin markers is extinguished in the sympathetic ganglia but retained by cells within the adrenal gland. Concomitant with the loss of the SA 1-5 immunoreactivity in sympathetic ganglia, a later sympathetic neuron-specific marker, B2, appears. In dissociated cell suspensions, some B2+ cells that coexpress SA 1 are seen. This implies a switch in the antigenic phenotype of developing sympathetic neurons, rather than a replacement of one cell population by another. The SA 1----B2 transition does not occur for the majority of cells within the adrenal primordium. In vitro, most B2+ cells fail to differentiate into chromaffin cells in response to glucocorticoid. Instead, they continue to extend neurites and then die. Taken together, these data imply that the SA 1----B2 transition correlates with a loss of competence to respond to an inducer of chromaffin differentiation. Thus, the development of SA derivatives is controlled both by environmental signals and by changes in the ability of differentiating cells to respond to such signals.

Deubiquitinating activity of CYLD is impaired by SUMOylation in neuroblastoma cells

“…1,2 Neuroblastoma originates from the sympathetic nervous system and is composed of undifferentiated and poorly differentiated neuroblasts arising from the different stages of sympathoadrenal lineage of neural crest origin. [2][3][4][5] Earlier reports have identified that in neuroblastoma the expression of markers that are upregulated in later stages of the neuronal lineage of sympathetic nervous system differentiation, such as neurotrophic tyrosine kinase, receptor, type 1 (NTRK1) and growth-associated protein 43 (GAP43), is indicative of better prognosis. 6,7 The age of patient, genetic aberrations (N-MYC amplification and deletion of chromosome 11 q) and metastatic spread are important factors with regard to treatment decision and patient prognosis.…”

“…[12][13][14] In addition, retinoids can also downregulate the expression of certain genes such as N-MYC, concurrent with the arrest of cell proliferation. 11,5,16 Elucidating the mechanisms behind the differentiation of neuroblastoma cells is therefore of clinical importance.…”

ZENON, a Novel POZ Kruppel-Like DNA Binding Protein Associated with Differentiation and/or Survival of Late Postmitotic Neurons

“…These cells are extremely diverse in their functional, morphological, and anatomical properties and have different embryonic origins. Depending on their locations in the adult central nervous system (CNS) and peripheral nervous system (PNS), catecholaminergic cells originate from different parts of the neural tube and neural crest (6,73,74). In the embryonic neural tube, catecholaminergic cell groups arise from various neuromeres (64, 78), suggesting that a large number of extracellular signals and transcription factors govern the specification and maintenance of catecholaminergic identity.…”

The Protumorigenic Role of Caspase-8 in Neuroblastoma

“…No such studies have been published for NB tumor growth in the CAM assay. NB7 cells with and without casp8, were seeded on the chorioallantoic membrane of fertilized chick eggs at a concentration of 5x10 6 cells per egg and tumors were harvested seven days later. In comparison, our orthotopic mouse model required 2x10 5 cells per mouse and up to ten weeks for tumor burden.…”

“…NB, considered to be a disease of the sympathetic nervous system, is derived from neural crest cells of the sympaticoadrenal lineage. Sympaticoadrenal cells give rise to the medullary region of the adrenal gland and the sympathetic ganglia [5,6]. NB may develop anywhere along the sympathetic axis including the neck (5%), chest (20%), pelvis (5%), and abdominal cavity (65%) of which the adrenal medulla is the most common site of tumorigenesis [3,7,8].…”