Expression pattern of delta-like 1 homolog in developing sympathetic neurons and chromaffin cells

Abstract

Delta-like 1 homolog (DLK1) is a member of the epidermal growth factor (EGF)-like family and an atypical notch ligand that is widely expressed during early mammalian development with putative functions in the regulation of cell differentiation and proliferation. During later stages of development, DLK1 is downregulated and becomes increasingly restricted to specific cell types, including several types of endocrine cells. DLK1 has been linked to various tumors and associated with tumor stem cell features. Sympathoadrenal precursors are neural crest derived cells that give rise to either sympathetic neurons of the autonomic nervous system or the endocrine chromaffin cells located in the adrenal medulla or extraadrenal positions. As these cells are the putative cellular origin of neuroblastoma, one of the most common malignant tumors in early childhood, their molecular characterization is of high clinical importance. In this study we have examined the precise spatiotemporal expression of DLK1 in developing sympathoadrenal cells. We show that DLK1 mRNA is highly expressed in early sympathetic neuron progenitors and that its expression depends on the presence of Phox2B. DLK1 expression becomes quickly restricted to a small subpopulation of cells in sympathetic ganglia, while virtually all chromaffin cells in the adrenal medulla and the Organ of Zuckerkandl still express high levels of DLK1 at late gestational stages.

Interplay between intrinsic reprogramming potential and microenvironment controls neuroblastoma cell plasticity and identity

“…We nevertheless disagree with their interpretation of cell phenotypes. We strongly believe that CARTPT and INSM1, used by Dong et al to define sympathoblast identity, rather witness a chromaffin-like phenotype, since they are co-expressed with DLK1, CDKN1C, CHGA/CHGB, TH, DBH and SLC18A1 in our data [25][26][27][40][41][42][43][44] . Integration of our single-cell RNA-seq data from 14 PDX models revealed two distinct cell populations expressing either markers of chromaffin cells or markers of sympathoblasts.…”

BET and CDK Inhibition Reveal Differences in the Proliferation Control of Sympathetic Ganglion Neuroblasts and Adrenal Chromaffin Cells

“…As the postnatal adrenal medulla is not only composed of chromaffin cells but also contains a low number of neuroblasts, it is important to define the identity of the cells isolated from sympathetic ganglia and adrenal [ 8 ]. Chromaffin cells are characterized by the expression of the pan-autonomic transcription factor PHOX2B, noradrenergic marker proteins such as TH and VMAT1, and genes that are selectively expressed in chromaffin cells but not in sympathetic neurons, such as Dlk1 , SgII , and Pnmt [ 62 , 63 , 64 ]. During development, some pan-neuronal genes are also co-expressed [ 62 ].…”

MEIS2 Is an Adrenergic Core Regulatory Transcription Factor Involved in Early Initiation of TH-MYCN-Driven Neuroblastoma Formation

“…Other strongly upregulated genes in this set were Dlk1 , highly expressed in early sympathetic neuron progenitors [ 54 ] and Plk1 , a known therapeutic target in neuroblastoma [ 55 ]. Gene ontology analysis on the set of protein-coding genes revealed among the upregulated genes an enrichment for cell cycle and DNA repair factors ( Figure 4 B, left, red bars ), while acetylcholine synthesis was shown to be downregulated, a neurotransmitter that is synthesized in some primary neuroblastomas ( Figure 4 B, left, blue bars ).…”