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.

Multipotent peripheral glial cells generate neuroendocrine cells of the adrenal medulla

“…S11B). The transient arrest in the proliferation of early differentiated TH + chromaffin cells is similar to that previously reported in developing sympathetic ganglia (4, 20). …”

“…The sympathoblasts were distinguished by the presence of Slc18a3 (19) and Cartpt (coding for CART) (4) as well as by broader markers of sympatho-adrenal differentiation such as Th and chromaffin cells were identified by a Th + /Phox2b + /Chgb + /Slc18a3 − /Cartpt − signature (Fig. 5C,H and Fig.…”

“…The more ventral group of cells forms the AM, while the dorsal portion coalesces into a sympathetic ganglion (SG) (1, 2). However, this view is challenged by the discovery of early differential expression of markers in the sympatho-adrenal lineage (3, 4) and the presence of SOX10 + satellite glial cells in the early sympathetic system at the time of adrenal anlagen formation (5, 6). Direct evidence on how the AM is formed is missing, and furthermore, the current idea does not explain the cellular origin of the suprarenal sympathetic ganglion (SRG), in direct association with the adrenal gland.…”

Schwann Cell Precursors Generate the Majority of Chromaffin Cells in Zuckerkandl Organ and Some Sympathetic Neurons in Paraganglia

“…However, several studies have lately challenged that idea. Firstly, the progenitors of the two systems seem to express discrete markers even before they reach the area of the dorsal aorta (Ernsberger et al, 2005; Chan et al, 2016). Furthermore, recent studies proved that the two cell types are of different origin, with the majority of adrenal chromaffin cells being derived late from nerve-associated multipotent cells, also known as Schwann cell precursors (SCPs), which use the axons of the preganglionic neurons as a pathway to the sympathoadrenal (SA) anlage (Furlan et al, 2017; Lumb et al, 2018).…”

Computational Mathematical Model Based on Lyapunov Function for the Hormonal Storage Control

“…In the study of the endocrine cells has been advances. Researches in animals using cell cultures developed to mimic events occurring in their dynamics have help to understand some mechanisms [10,30,33,40]. Undoubtedly, mathematical and computational modeling is a path that can help a lot in this understanding, providing answers to many questions generated by experimental research.…”