Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development

Arman, Esther; Haffner-Krausz, Rebecca; Chen, Yali; Heath, John K.; Lonai, Peter

doi:10.1073/pnas.95.9.5082

Cited by 574 publications

(419 citation statements)

References 39 publications

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“…Mice lacking either Fgf4 or Fgf receptor2 (Fgfr2) do not form PE in vivo or in vitro (Feldman et al, 1995;Wilder et al, 1997;Arman et al, 1998). Overexpression of a dominant-negative form of the Fgf receptor prevents formation of PE in vitro in embryoid bodies (Li et al, 2001).…”

Section: Molecular Regulation Of Epi/ Pe Lineage Formationmentioning

confidence: 99%

Cell and molecular regulation of the mouse blastocyst

Yamanaka

Ralston

Stephenson

et al. 2006

Developmental Dynamics

265

221

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Animals use diverse strategies to specify tissue lineages during development. A common strategy is to partition maternally supplied and localized lineage determinants into progenitor cells. The mouse embryo appears to use a different, more regulative strategy to specify the first three lineages: the epiblast (EPI: future embryo), the trophectoderm (TE: future placenta), and the primitive endoderm (PE: future yolk sac). These lineages are specified during two successive differentiation steps leading to formation of the blastocyst. Here, we review classic and contemporary models of early lineage specification in the mouse, and describe recent efforts to understand the molecular regulation of these events. We describe evidence that trophectoderm differentiation bears resemblance to the process of epithelialization and describe the importance of apical/basal protein complexes in regulating this process. Next, we present a revised model of PE specification, and describe evidence that PE cells in the inner cell mass sort out to occupy their ultimate position on the surface of the EPI. Finally, we describe factors that reinforce these lineages and three distinct stem cell types that can be isolated from them. Together, these mechanisms guide the differentiation of the first lineages of the mouse and thereby set up tissues that will be important for the first steps of embryonic body patterning. Developmental Dynamics 235:2301-2314, 2006.

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Section: Molecular Regulation Of Epi/ Pe Lineage Formationmentioning

confidence: 99%

Cell and molecular regulation of the mouse blastocyst

Yamanaka

Ralston

Stephenson

et al. 2006

Developmental Dynamics

265

221

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“…ES cells were cultured as described before (Arman et al, 1998). In all experiments the ROSA11 ES cell line was used.…”

Section: Es Cells and Embryoid Body Culturesmentioning

confidence: 99%

Fibroblast growth factor (FGF) signaling through PI 3-kinase and Akt/PKB is required for embryoid body differentiation

et al. 2000

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The role of FGF signaling in early epithelial di erentiation was investigated in ES (embryonic stem) cell derived embryoid bodies. A dominant negative ®broblast growth factor receptor (FGFR) mutation was created by stably introducing into ES cells an Fgfr2 cDNA, truncated in its enzymatic domains. These cells failed to di erentiate into cystic embryoid bodies. No epithelial di erentiation and cavitation morphogenesis could be observed, in the mutant, although its rate of cell proliferation remained unchanged. This phenotype was associated with a signi®cant decrease in the activation of Akt/PKB and PLCg-1, as compared to the wild type, while the activation of MAPK/Erk was less a ected. Requirement for PI 3-kinase signaling in embryoid body di erentiation was demonstrated by speci®c inhibitors. Akt/PKB activation was abrogated by wortmannin in short-term experiments. In long-term cultures Ly294002 inhibited the di erentiation of ES cells into embryoid bodies. Our data demonstrate that for early epithelial di erentiation FGF signaling is required through the PI 3-kinase-Akt/ PKB pathway.

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“…Mice with a targeted deletion of the transmembrane and a portion of the TK domain of Fgfr2 die at E4.5-5.5 (Arman et al, 1998), while embryos carrying a targeted disruption of the Fgfr2b isoform die at birth, primarily due to a failure of lung formation (De Moerlooze et al, 2000;Revest et al, 2001). In contrast, mouse embryos with a homozygous deletion of Fgfr2 Ig domain III (Fgfr2 ⌬lgIII/⌬lgIII ), which is shared by both FGFR2b and FGFR2c isoforms, died at E10.5 due to placental defects .…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, mouse embryos with a homozygous deletion of Fgfr2 Ig domain III (Fgfr2 ⌬lgIII/⌬lgIII ), which is shared by both FGFR2b and FGFR2c isoforms, died at E10.5 due to placental defects . Analysis of these mutant embryos revealed that FGFR2 is essential for induction and patterning of multiple organs, including limb, lung, inner ear, placenta, and skin (Arman et al, 1998(Arman et al, , 1999De Moerlooze et al, 2000;Pirvola et al, 2000;Revest et al, 2001;Xu et al, 1998). A similar observation was also made in embryos that overexpress a dominant-negative secreted Fgfr2 (Celli et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor receptor 2 (Fgfr2) plays an important role in eyelid and skin formation and patterning

Guo

et al. 2001

Developmental Dynamics

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Initiating as protruding ridges above and below the optic vesicle, the eyelids of mice grow across the eye and temporarily fuse in fetal life. Mutations of a number of genes disrupt this developmental process and result in a birth defect, "open-eyelids at birth." Here we show that a critical event for eyelid induction occurs at embryonic day 11.5 (E11.5) when the single cell-layered ectoderm in the presumptive eyelid territory increases proliferation and undergoes morphologic transition to form cube-shaped epithelial cells. Using embryos lacking the Fgfr2 Ig domain III (Fgfr2 ⌬III/⌬III ) generated by tetraploid rescue and chimeric embryo formation approaches, we demonstrate that this event is controlled by Fgfr2 signals as the Fgfr2 ⌬III/⌬III mutation blocks these changes and results in embryos without eyelids. Fgfr2 and its ligands are differentially expressed in the ectoderm and underlying mesenchyme and function in a reciprocal interacting loop that specifies eyelid development. We also demonstrate that similar defects account for failure of skin formation at early stages. Interestingly, Fgfr2-independent skin formation occurs at E14.5 mutant embryos, resulting in much thinner, yet well-differentiated epidermis. Notably, mutant skin remains thin with decreased hair density after transplantation to wild-type recipients. These data demonstrate an essential role of Fgfr2 in eyelid and skin formation and patterning. Published 2001 Wiley-Liss, Inc. †

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Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development

Cited by 574 publications

References 39 publications

Cell and molecular regulation of the mouse blastocyst

Cell and molecular regulation of the mouse blastocyst

Fibroblast growth factor (FGF) signaling through PI 3-kinase and Akt/PKB is required for embryoid body differentiation

Fibroblast growth factor receptor 2 (Fgfr2) plays an important role in eyelid and skin formation and patterning

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