Role for FGFR2IIIb-mediated signals in controlling pancreatic endocrine progenitor cell proliferation

Elghazi, Lynda; Cras-Méneur, Corentin; Czernichow, P; Scharfmann, Raphaël

doi:10.1073/pnas.062321799

Cited by 116 publications

(101 citation statements)

References 39 publications

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“…It is significant for the discussion here that the pancreatic progenitor population that expands in response to FGFR2IIIb ligands in vitro also displays an arrest in further differentiation (Hart et al, 2003;Norgaard et al, 2003). This arrest is reversible; upon removal of FGF7, pancreatic progenitor cells expanded by this cytokine in vitro differentiate en mass to become endocrine cells (Elghazi et al, 2002).…”

Section: Discussionmentioning

confidence: 98%

FGFR2IIIb signaling regulates thymic epithelial differentiation

Dooley

Erickson

LaRochelle

et al. 2007

Developmental Dynamics

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Heterogeneous epithelial populations comprising the thymic environment influence early and late stages of T-cell development. The processes that regulate the differentiation of thymic epithelium and that are responsible for this heterogeneity are not well understood, although mesenchymal/epithelial interactions are clearly involved. Here, we show that targeted expression by thymocytes of an fibroblast growth factor receptor-2IIIb (FGFR2IIIb) ligand, FGF10, profoundly alters the differentiation and function of thymic epithelium (TE). Reconstitution of irradiated lckFGF10 mice with normal bone marrow restores normal thymic organization and function, while wild-type mice reconstituted with lckFGF10 bone marrow recapitulates some of the thymic alterations seen in lckFGF10 mice. We also demonstrate that interference with FGFR2IIIb signaling in the thymus with a soluble FGFR2IIIb dominant-negative fusion protein leads to precocious reductions in thymic size and cellularity that resemble age-related thymic involution. These findings indicate that TE compartments are dynamically maintained and that FGF signals are involved in this process. Developmental Dynamics 236:3459 -3471, 2007.

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Section: Discussionmentioning

confidence: 98%

FGFR2IIIb signaling regulates thymic epithelial differentiation

Dooley

Erickson

LaRochelle

et al. 2007

Developmental Dynamics

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“…The in vitro approach of pancreatic rudiment development is frequently used to study growth factor effects on beta cell development [37][38][39]. The mitogenic effect of IGFs on beta cells is well established [7].…”

Section: Discussionmentioning

confidence: 99%

Defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly in the Goto–Kakizaki rat model of type 2 diabetes

et al. 2007

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Aims/hypothesis The Goto-Kakizaki (GK) rat is a spontaneous model of type 2 diabetes. Defective beta cell mass detectable in late fetal age precedes the onset of hyperglycaemia. Our hypothesis was that an embryonic IGF production deficiency might be involved in beta cell mass anomaly in the diabetic GK rat. To test this, we evaluated during pancreatic organogenesis: (1) the beta cell development in GK rats on embryonic day (E) 13.5 and E18.5; (2) IGF2 and IGF1 receptor (IGF1R) pancreatic protein production on E13.5 and E18.5; (3) the in vitro development of GK pancreatic rudiment on E13.5; and (4) the in vitro effect of IGF2 addition on beta cell mass. Materials and methods Beta cell quantitative analyses were determined by immunohistochemistry and morphometry. IGF2 and IGF1R pancreatic protein production was evaluated using western blot analyses. Dorsal pancreatic rudiments were dissected on E13.5, separated from surrounding mesenchyme and cultured for 7 days without or with recombinant IGF2. Results While beta cell mass was already decreased on E18.5, the differentiation of the first beta cells was in fact normal in E13.5 GK pancreas. Moreover, defective IGF2 and IGF1R protein production was detected in GK pancreatic rudiment as early as E13.5. The isolated GK pancreatic rudiment as maintained in vitro mimics the GK beta cell deficiency observed in vivo. This last approach enabled us to show that GK beta cells were fully responsive to IGF2 as far as their net growth is concerned. Conclusions/interpretation In diabetic GK rat, defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly. IGF2 supplementation expands the pool of beta cells.

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“…In the absence of mesenchyme, growth and morphogenesis of the pancreatic buds are severely impaired and the epithelium undergoes a "default" endocrine differentiation at the expense of exocrine acinar formation (Gittes et al, 1996;Miralles et al, 1998). Recent studies suggest that fibroblast growth factors and the mitogen-activated protein kinase signaling pathway are involved in mediating this interaction between mesenchyme and epithelium (Bhushan et al, 2001;Elghazi et al, 2002). However, the factors that confer the property to promote exocrine differentiation to the pancreatic mesenchyme remain to be studied.…”

Section: Introductionmentioning

confidence: 99%

Expression of Sox transcription factors in the developing mouse pancreas

Lioubinski¹,

Müller²,

Wegner

et al. 2003

Developmental Dynamics

113

128

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Previous work has identified members of the homeodomain and basic helix-loop-helix families of transcription factors as critical determinants of mammalian pancreatic development. Here, we describe the identification of HMG-box transcription factors of the Sox gene family in the mouse pancreas. We detected transcripts for Sox11, Sox4, Sox13, Sox5, Sox9, Sox8, Sox10, Sox7, Sox17, Sox18, Sox15, and Sox30 in embryonic pancreas and found Sox4, Sox9, and Sox13 in adult pancreatic islets. Expression of seven of these Sox factors was studied in more detail by in situ hybridization from the stage of early pancreatic outgrowth to birth. Expression of Sox11 was found in the mesenchyme surrounding the pancreatic buds, whereas Sox4 and Sox9 were confined to the pancreatic epithelium and later to islets. Sox13 and L-Sox5 showed expression in most of the pancreatic epithelial cells between embryonic days 12.5 and 14.5. Sox8 and Sox10 were detected in a thin layer of cells surrounding the islets. The expression patterns of Sox genes in the embryonic pancreas suggest that they could have important and possibly redundant functions in pancreas development. Developmental Dynamics 227:402-408, 2003.

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Role for FGFR2IIIb-mediated signals in controlling pancreatic endocrine progenitor cell proliferation

Cited by 116 publications

References 39 publications

FGFR2IIIb signaling regulates thymic epithelial differentiation

FGFR2IIIb signaling regulates thymic epithelial differentiation

Defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly in the Goto–Kakizaki rat model of type 2 diabetes

Expression of Sox transcription factors in the developing mouse pancreas

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