Exogenous FGF10 can rescue an eye‐open at birth phenotype of <i>Fgf10</i>‐null mice by activating activin and TGFα‐EGFR signaling

Tao, Hirotaka; Ono, Katsuhiko; Kurose, Hitomi; Noji, Sumihare; Ohuchi, Hideyo

doi:10.1111/j.1440-169x.2006.00869.x

Cited by 20 publications

(23 citation statements)

References 29 publications

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“…32,35,49 It would seem plausible to suggest that “repair recapitulates morphogenesis” with almost identical cytoskeletal machinery. 33 One single remarkable exception is that eyelid morphogenesis usually results in a perfect outcome, whereas the final outcome in adult wound healing may involve an inflammatory response and result in scarring and tissue deformity. This could be an evolutionary response to protect adults against microbial invasion if the skin barrier is broken, whereas the sealed environment of the embryo does not require such protection against infection.…”

Section: Discussionmentioning

confidence: 99%

“…7,10,31 The leading edge cells extend filopodia that scan and help make contact with the advancing edge of the opposing eyelid. 32,33 When a connection is established between both sides, the periderm cells flatten again and form a continuous sheet, ultimately covering the cornea. This process of eyelid fusion involves 2 coordinated yet distinct processes: epithelial cell migration and proliferation of the epithelium at the migrating edge (Fig.…”

Section: The Eyelid During the Embryonic Stagementioning

confidence: 99%

See 1 more Smart Citation

Embryologic and Fetal Development of the Human Eyelid

Tawfik¹,

Abdulhafez²,

Fouad

et al. 2016

Ophthalmic Plastic &Amp; Reconstructive Surgery

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Purpose:To review the recent data about eyelid morphogenesis, and outline a timeline for eyelid development from the very early stages during embryonic life till final maturation of the eyelid late in fetal life.Methods:The authors extensively review major studies detailing human embryologic and fetal eyelid morphogenesis. These studies span almost a century and include some more recent cadaver studies. Numerous studies in the murine model have helped to better understand the molecular signals that govern eyelid embryogenesis. The authors summarize the current findings in molecular biology, and highlight the most significant studies in mice regarding the multiple and interacting signaling pathways involved in regulating normal eyelid morphogenesis.Results:Eyelid morphogenesis involves a succession of subtle yet strictly regulated morphogenetic episodes of tissue folding, proliferation, contraction, and even migration, which may occur simultaneously or in succession.Conclusions:Understanding the extraordinary process of building eyelid tissue in embryonic life, and deciphering its underlying signaling machinery has far reaching clinical implications beyond understanding the developmental abnormalities involving the eyelids, and may pave the way for achieving scar-reducing therapies in adult mammalian wounds, or control the spread of malignancies.

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Section: Discussionmentioning

confidence: 99%

Section: The Eyelid During the Embryonic Stagementioning

confidence: 99%

Embryologic and Fetal Development of the Human Eyelid

Tawfik¹,

Abdulhafez²,

Fouad

et al. 2016

Ophthalmic Plastic &Amp; Reconstructive Surgery

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“…S1C). Concomitantly, several eyelid morphogens are also abundantly expressed in the protruding tip of the developing eyelids, raising the possibility that some of the morphogenic signals induce MAP3K1 expression (5,21,22). To test this possibility, we treated the Map3k1 ΔKD/ΔKD cells with morphogenetic factors, including: TGF-α and EGF, which activate EGFR; activin B and TGF-β1, which act through receptors of the TGF-β superfamily; FGF10, which act through a FGF receptor; and retinoic acid, which acts through RXR, and measured β-gal activity ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) integrates developmental signals for eyelid closure

Geh¹,

Meng²,

Mongan³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Developmental eyelid closure is an evolutionarily conserved morphogenetic event requiring proliferation, differentiation, cytoskeleton reorganization, and migration of epithelial cells at the tip of the developing eyelid. Many signaling events take place during eyelid closure, but how the signals converge to regulate the morphogenetic process remains an open and intriguing question. Here we show that mitogen-activated protein kinase kinase kinase 1 (MAP3K1) highly expressed in the developing eyelid epithelium, forms with c-Jun, a regulatory axis that orchestrates morphogenesis by integrating two different networks of eyelid closure signals. A TGF-α/EGFR-RhoA module initiates one of these networks by inducing c-Jun expression which, in a phosphorylation-independent manner, binds to the Map3k1 promoter and causes an increase in MAP3K1 expression. RhoA knockout in the ocular surface epithelium disturbs this network by decreasing MAP3K1 expression, and causes delayed eyelid closure in Map3k1 hemizygotes. The second network is initiated by the enzymatic activity of MAP3K1, which phosphorylates and activates a JNK-c-Jun module, leading to AP-1 transactivation and induction of its downstream genes, such as Pai-1 . MAP3K1 inactivation reduces AP-1 activity and PAI-1 expression both in cells and developing eyelids. MAP3K1 is therefore the nexus of an intracrine regulatory loop connecting the TGF-α/EGFR/RhoA-c-Jun and JNK-c-Jun-AP-1 pathways in developmental eyelid closure.

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“…Mouse eyelid formation begins at around embryonic day 11.5 (E11.5). At this time, the surface ectoderm adjacent to the developing cornea folds to form the lid buds, which are a simple structure consisting of loose periocular mesenchyme (POM) covered by undifferentiated ectoderm [3]–[6]. The eyelid buds grow from E12 onward, and they extend across the ocular surface, undergoing proliferation and differentiation.…”

Section: Introductionmentioning

confidence: 99%

Expression of Signaling Components in Embryonic Eyelid Epithelium

et al. 2014

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Closure of an epithelium opening is a critical morphogenetic event for development. An excellent example for this process is the transient closure of embryonic eyelid. Eyelid closure requires shape change and migration of epithelial cells at the tip of the developing eyelids, and is dictated by numerous signaling pathways. Here we evaluated gene expression in epithelial cells isolated from the tip (leading edge, LE) and inner surface epithelium (IE) of the eyelid from E15.5 mouse fetuses by laser capture microdissection (LCM). We showed that the LE and IE cells are different at E15.5, such that IE had higher expression of muscle specific genes, while LE acquired epithelium identities. Despite their distinct destinies, these cells were overall similar in expression of signaling components for the “eyelid closure pathways”. However, while the LE cells had more abundant expression of Fgfr2, Erbb2, Shh, Ptch1 and 2, Smo and Gli2, and Jag1 and Notch1, the IE cells had more abundant expression of Bmp5 and Bmpr1a. In addition, the LE cells had more abundant expression of adenomatosis polyposis coli down-regulated 1 (Apcdd1), but the IE cells had high expression of Dkk2. Our results suggest that the functionally distinct LE and IE cells have also differential expression of signaling molecules that may contribute to the cell-specific responses to morphogenetic signals. The expression pattern suggests that the EGF, Shh and NOTCH pathways are preferentially active in LE cells, the BMP pathways are effective in IE cells, and the Wnt pathway may be repressed in LE and IE cells via different mechanisms.

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Exogenous FGF10 can rescue an eye‐open at birth phenotype of Fgf10‐null mice by activating activin and TGFα‐EGFR signaling

Cited by 20 publications

References 29 publications

Embryologic and Fetal Development of the Human Eyelid

Embryologic and Fetal Development of the Human Eyelid

Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) integrates developmental signals for eyelid closure

Expression of Signaling Components in Embryonic Eyelid Epithelium

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