Source and Impact of the EGF Family of Ligands on Intestinal Stem Cells

Abstract

Epidermal Growth Factor (EGF) has long been known for its role in promoting proliferation of intestinal epithelial cells. EGF is produced by epithelial niche cells at the base of crypts in vivo and is routinely added to the culture medium to support the growth of intestinal organoids ex vivo. The recent identification of diverse stromal cell populations that reside underneath intestinal crypts has enabled the characterization of key growth factor cues supplied by these cells. The nature of these signals and how they are delivered to drive intestinal epithelial development, daily homeostasis and tissue regeneration following injury are being investigated. It is clear that aside from EGF, other ligands of the family, including Neuregulin 1 (NRG1), have distinct roles in supporting the function of intestinal stem cells through the ErbB pathway.

SpatialDM: Rapid identification of spatially co-expressed ligand-receptor reveals cell-cell communication patterns

“…Table 7). The EGF pathway comprises diverse ligands (including EGF, TGFA, AREG, EREG, and HBEGF) and receptors (including EGFR, ERBB2, ERBB3, and ERBB4), exerting distinct or redundant functions [33]. In the adult sample we analyzed, most EGF interactions were detected and enriched in pattern 1 (Fig.…”

“…As reported, the EGF signalling plays important roles primarily in intestinal epithelial cell proliferation and self-renewal, and has a complex interplay with other pathways [33]. Nászai, et al have revealed that RAL GTPases, encoded by RALA and RALB, are necessary and sufficient to activate EGFR signalling and further MAPK signalling in the intestine [34].…”

A novel epidermal growth factor‐like domain protein 6 from Apostichopus japonicus mediates coelomocyte proliferation

“…The ORF encoded putative 829 aa, 91.02 kDa protein with a predicted N‐terminal signal peptide and five centrally located EGF‐like domains (Figure 1), with the second domain belonging to a subclass of EGF‐like domains that bind Ca 2+ . Furthermore, a region with similarity to the DSL domain that is conserved in ligands of Notch receptors (Abud et al, 2021; Lindsell et al, 1995) was detected within the first EGF‐like domain. The presence of a signal peptide sequence suggested that the AjEGFL6 protein was secreted.…”

“…EGFL proteins are characterized by their multiple EGF repeats, which consist of 30-40 amino acid (aa) residues possessing remarkable homology to EGF, EGF repeats are an evolutionarily conserved domain with six cysteines forming three disulphide bonds (Downing et al, 1996). Due to the EGF-like domain being highly homologous to EGF, the members of the EGFL family also share common functional characteristics with EGF; all of which could play biological roles by binding to a group of transmembrane tyrosine kinase receptors, such as epidermal growth factor receptor EGFR 1-4 (Abud et al, 2021). In vertebrates, several EGFL family members have been identified, including EGFL2, EGFL3, EGFL5, EGFL6, EGFL7, EGFL8 and EGFL9.…”

Role of ErbB1 in the Underlying Mechanism of Lapatinib-Induced Diarrhoea: A Review

“…Specifically, all these ErbBs can be found abundantly in small intestinal cells but have lower expression in Paneth cells [ 21 ]. However, a study using single-cell mapping showed no expression of ErbB4 throughout the epithelium [ 22 ], but both EGF and NRG1-expressing cells were identified in the developing human intestinal tract, with EGF being found in the epithelial villus domain and NRG1 being discovered in cells inside the subepithelial mesenchyme underneath the crypts [ 23 ].…”