DLK1 Protein Expression during Mouse Development Provides New Insights into Its Function

Falix, Farah A.; Tjon-A-Loi, M. R. S.; Gaemers, Ingrid C.; Aronson, Daniël C.; Lamers, W. H.

doi:10.1155/2013/628962

Cited by 14 publications

(14 citation statements)

References 42 publications

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“…In support of this, asymmetric expression of Dlk1 at the peripheral OE is reminiscent of Sox2 expression in this tissue (Chen et al, 2009). A recent study used section IHC to detect DLK1 protein expression at similar stages to those reported here (Falix et al, 2013), and identified protein expression in many of the same structures during early embryogenesis. These results are complementary, as together these studies allow us to assess both protein and RNA expression in embryonic sections as well as in whole mounts.…”

Section: Discussionsupporting

confidence: 59%

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Multiple Dlk1 splice variants are expressed during early mouse embryogenesis

Miller¹,

Cole²

2014

Int. J. Dev. Biol.

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Delta-like homologue 1 (Dlk1), an atypical Notch ligand, is known to have roles in growth and development, stem cell maintenance, and cancer. Evidence suggests that Dlk1 expression patterns are more complex than previously appreciated, with multiple isoforms expressed in various tissues in both the embryo and adult. However, the early embryonic expression of Dlk1 has not been well examined. Given that tissue specific Dlk1 knockouts have to date failed to recapitulate phenotypes associated with the conventional Dlk1 loss of function model, a better understanding of early Dlk1 expression is important. To address this question, we have examined Dlk1 expression during the early stages of mouse embryogenesis. Dlk1 expression was first detected at Theiler Stage 14 (TS14), and its expression pattern persisted in specific tissues through TS20. Further, we found that all known Dlk1 splice isoforms were expressed in early embryogenesis, with Dlk1-A and Dlk1-C/C2 isoforms being expressed at the highest levels. The broad co-expression of multiple Dlk1 isoforms corroborates recent work suggesting that Dlk1-mediated signaling may act through multiple DLK1 isoforms to balance differentiation.

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Section: Discussionsupporting

confidence: 59%

“…Given these facts, and the finding that DLK1 protein expression can be observed as early as E10 (Falix et al, 2013), we performed a study of Dlk1 expression during early mouse embryogenesis. Here, we demonstrate that Dlk1 expression is detectable as early as Theiler Stage 13 (TS13, E8.5 on our background).…”

mentioning

confidence: 99%

Multiple Dlk1 splice variants are expressed during early mouse embryogenesis

Miller¹,

Cole²

2014

Int. J. Dev. Biol.

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“…; Falix et al . ). Suggestively, the majority of the transcription regulatory element of DLK1 is localized ca .…”

Section: Resultsmentioning

confidence: 97%

Genomic variation at the tips of the adaptive radiation of Darwin's finches

et al. 2016

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Adaptive radiation unfolds as selection acts on the genetic variation underlying functional traits. The nature of this variation can be revealed by studying the tips of an ongoing adaptive radiation. We studied genomic variation at the tips of the Darwin's finch radiation; specifically focusing on polymorphism within, and variation among, three sympatric species of the genus Geospiza. Using restriction site-associated DNA (RAD-seq), we characterized 32 569 single-nucleotide polymorphisms (SNPs), from which 11 outlier SNPs for beak and body size were uncovered by a genomewide association study (GWAS). Principal component analysis revealed that these 11 SNPs formed four statistically linked groups. Stepwise regression then revealed that the first PC score, which included 6 of the 11 top SNPs, explained over 80% of the variation in beak size, suggesting that selection on these traits influences multiple correlated loci. The two SNPs most strongly associated with beak size were near genes associated with beak morphology across deeper branches of the radiation: delta-like 1 homologue (DLK1) and high-mobility group AT-hook 2 (HMGA2). Our results suggest that (i) key adaptive traits are associated with a small fraction of the genome (11 of 32 569 SNPs), (ii) SNPs linked to the candidate genes are dispersed throughout the genome (on several chromosomes), and (iii) micro- and macro-evolutionary variation (roots and tips of the radiation) involve some shared and some unique genomic regions.

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“…DLK1 is a non-canonical notch ligand interacting with the Delta-Notch signaling pathway, which is involved in cell fate decisions, progenitor maintenance and cell differentiation (Bray, 2006;Fiúza and Arias, 2007;D'Souza et al, 2010). DLK1 is widely expressed during embryonic development of mammals (Falix et al, 2013), but in the adult its expression is downregulated and highly restricted to certain organs, including adrenal chromaffin cells (Jensen et al, 1993;Larsen et al, 1996;Hedlund et al, 2003). Despite its widespread expression during embryonic development, mice carrying deletions of DLK1 display relatively mild deficits, including a partially penetrant neonatal lethality, growth retardation, skeletal deficits and accelerated adiposity (Moon et al, 2002;Appelbe et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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

Faitwri

Huber

2018

Gene Expression Patterns

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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.

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DLK1 Protein Expression during Mouse Development Provides New Insights into Its Function

Cited by 14 publications

References 42 publications

Multiple Dlk1 splice variants are expressed during early mouse embryogenesis

Multiple Dlk1 splice variants are expressed during early mouse embryogenesis

Genomic variation at the tips of the adaptive radiation of Darwin's finches

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

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