Fibroblast growth factor receptor-3 regulates Paneth cell lineage allocation and accrual of epithelial stem cells during murine intestinal development

Vidrich, Alda; Buzan, Jenny M.; Brodrick, Brooks; Ilo, Chibuzo; Bradley, Leigh; Fendig, Kirstin Skaar; Sturgill, Thomas W.; Cohn, Steven M.

doi:10.1152/ajpgi.90589.2008

Cited by 47 publications

(51 citation statements)

References 50 publications

(67 reference statements)

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“…By postnatal day 21, FGFR-3 Ϫ/Ϫ mice show a marked deficit in a number of Paneth cell markers and a significant reduction in the number of lysozyme-positive Paneth cells. Additionally, these mice also have a reduced number of intestinal crypts compared with wild-type mice that is a reflection of diminished numbers of crypt stem cells (13). These data suggest that FGFR-3-mediated signaling events play a role in the developmental regulation of the stem cell compartment as well as in the commitment of progenitor cells to Paneth cell lineage-specific differentiation.…”

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confidence: 83%

“…We recently reported that signaling through FGFR-3 in crypt epithelial cells regulates both the number of epithelial stem cells and Paneth cell differentiation during postnatal gut development (13,15). FGFR-3 is highly expressed along the membranes of cells in the lower portion of the crypt in the developing mouse intestine (15).…”

Section: Fibroblast Growth Factor Receptor-3 (Fgfr-mentioning

confidence: 99%

“…Cell Genes in Caco2 Cells-We previously reported that mice globally lacking functional FGFR-3 manifest a deficit in the number of Paneth cells in the small intestine during postnatal gut development, suggesting that FGFR-3 signaling is critical for the differentiation and/or maturation of these cells (13). To assess whether activation of FGFR-3-mediated signaling in intestinal epithelial cells directly affected expression of differentiation markers characteristic of the mature Paneth cell lineage, we first examined whether ligands of FGFR-3 could affect the expression of such markers in several intestinal epithelial cell lines (supplemental Fig.…”

Section: Ligands For Fgfr-3 Induce Expression Of Intestinal Panethmentioning

confidence: 99%

“…Studies using transgenic mice or mice with targeted mutations in epithelial regulatory genes, including components of the Wnt signaling pathway (Tcf4, Fz5, Sox9, and Apc), FGFR-3, and PPAR␤/␦, have identified these genes as key regulators of Paneth cell differentiation and expression of defensin peptides in vivo (9 -14). However, the lack of an adequate intestinal epithelial cell culture system that can recapitulate features of Paneth cell differentiation and maturation has hampered direct investigation of how these signaling pathways may interact in regulating Paneth cell differentiation and functional maturation.We recently reported that signaling through FGFR-3 in crypt epithelial cells regulates both the number of epithelial stem cells and Paneth cell differentiation during postnatal gut development (13,15). FGFR-3 is highly expressed along the membranes of cells in the lower portion of the crypt in the developing mouse intestine (15).…”

mentioning

confidence: 99%

“…Thus, the Wnt signal in Paneth cells, delivered by the Frizzled-5 (Fz5) receptor, drives cellular maturation of Paneth cells that have been allocated to that lineage. Although Wnt is the most well known regulator of TCF4/␤-catenin signaling, other growth factors, such as the FGFR-3 ligands FGF2 and FGF9, can also mediate signaling via this pathway (13,20).…”

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confidence: 99%

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Fibroblast Growth Factor Receptor-3 (FGFR-3) Regulates Expression of Paneth Cell Lineage-specific Genes in Intestinal Epithelial Cells through both TCF4/β-Catenin-dependent and -independent Signaling Pathways

Brodrick

Vidrich

Porter

et al. 2011

Journal of Biological Chemistry

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Fibroblast growth factor receptor-3 (FGFR-3Despite the critical importance of Paneth cells in maintaining gut homeostasis, knowledge of the pathways regulating Paneth cell differentiation and function has only recently begun to emerge. Studies using transgenic mice or mice with targeted mutations in epithelial regulatory genes, including components of the Wnt signaling pathway (Tcf4, Fz5, Sox9, and Apc), FGFR-3, and PPAR␤/␦, have identified these genes as key regulators of Paneth cell differentiation and expression of defensin peptides in vivo (9 -14). However, the lack of an adequate intestinal epithelial cell culture system that can recapitulate features of Paneth cell differentiation and maturation has hampered direct investigation of how these signaling pathways may interact in regulating Paneth cell differentiation and functional maturation.We recently reported that signaling through FGFR-3 in crypt epithelial cells regulates both the number of epithelial stem cells and Paneth cell differentiation during postnatal gut development (13,15). FGFR-3 is highly expressed along the membranes of cells in the lower portion of the crypt in the developing mouse intestine (15). FGFRs are members of the receptor-tyrosine kinase family. Ligand binding induces dimerization, autophosphorylation, and initiation of a signal transduction cascade that ultimately results in modification of gene expression. Ligands for FGFR-3, FGF1, FGF2, and FGF9, are up-regulated in the postnatal murine small intestine from birth through the suckling weaning transition, when crypt mor-

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mentioning

confidence: 83%

Section: Fibroblast Growth Factor Receptor-3 (Fgfr-mentioning

confidence: 99%

Section: Ligands For Fgfr-3 Induce Expression Of Intestinal Panethmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Fibroblast Growth Factor Receptor-3 (FGFR-3) Regulates Expression of Paneth Cell Lineage-specific Genes in Intestinal Epithelial Cells through both TCF4/β-Catenin-dependent and -independent Signaling Pathways

Brodrick

Vidrich

Porter

et al. 2011

Journal of Biological Chemistry

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Paneth cells and their multiple functions

Barreto

Rattes

Costa

et al. 2022

Cell Biology International

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The small intestine mucosa is lined by specialized cells that form the crypt-villus axis, which expands its surface. Among the six intestinal epithelial cell types, the Paneth cell is located at the base of the crypt, and it contains numerous granules in its cytoplasm, composed of antimicrobial peptides, such as defensins and lysozyme, and growth factors, such as epidermal growth factor, transforming growth factor-α, and Wnt ligands. Together, these elements act in the defense against microorganisms, regulation of intestinal microbiota, maintenance, and regulation of stem cell identity.Pathologies that target Paneth cells can disturb such defense activity, but they also affect the maintenance of the stem cell niche. In that way, Crohn's disease, necrotizing enterocolitis, and graft-versus-host disease promote a reduction of Paneth cell population, and, consequently, secretion of their products into the lumen of the crypts, making the affected organism predisposed to infections and dysbiosis. Additionally, the emergence of new intestinal cells is also decreased. This review aims to address the main characteristics of Paneth cells, highlighting their multiple functions and the importance of their preservation to ensure bowel homeostasis.

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Vertebrate intestinal endoderm development

Spence

Lauf

Shroyer

2011

Developmental Dynamics

173

157

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The endoderm gives rise to the lining of the esophagus, stomach and intestines, as well as associated organs. To generate a functional intestine, a series of highly orchestrated developmental processes must occur. In this review, we attempt to cover major events during intestinal development from gastrulation to birth, including endoderm formation, gut tube growth and patterning, intestinal morphogenesis, epithelial reorganization, villus emergence, as well as proliferation and cytodifferentiation. Our discussion includes morphological and anatomical changes during intestinal development as well as molecular mechanisms regulating these processes. Developmental Dynamics 240:501-520,

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Fibroblast growth factor receptor-3 regulates Paneth cell lineage allocation and accrual of epithelial stem cells during murine intestinal development

Cited by 47 publications

References 50 publications

Fibroblast Growth Factor Receptor-3 (FGFR-3) Regulates Expression of Paneth Cell Lineage-specific Genes in Intestinal Epithelial Cells through both TCF4/β-Catenin-dependent and -independent Signaling Pathways

Fibroblast Growth Factor Receptor-3 (FGFR-3) Regulates Expression of Paneth Cell Lineage-specific Genes in Intestinal Epithelial Cells through both TCF4/β-Catenin-dependent and -independent Signaling Pathways

Paneth cells and their multiple functions

Vertebrate intestinal endoderm development

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