Talk:Integumentary System - Eyelid Development

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On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes: References - recent and historic that relates to the topic Additional topic information - currently prepared in draft format Links - to related webpages Topic page - an edit history as used on other Wiki sites Lecture/Practical - student feedback Student Projects - online project discussions. Links: Pubmed Most Recent | Reference Tutorial | Journal Searches Glossary Links Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link Cite this page: Hill, M.A. (2024, April 30) Embryology Integumentary System - Eyelid Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Integumentary_System_-_Eyelid_Development

2016

Molecular biology and genetics of embryonic eyelid development

Ophthalmic Genet. 2016 Sep;37(3):252-9. doi: 10.3109/13816810.2015.1071409. Epub 2016 Feb 11.

Rubinstein TJ1, Weber AC1, Traboulsi EI1.

Abstract

The embryology of the eyelid is a complex process that includes interactions between the surface ectoderm and mesenchymal tissues. In the mouse and human, the eyelids form and fuse before birth; they open prenatally in the human and postnatally in the mouse. In the mouse, cell migration is stimulated by different growth factors such as FGF10, TGF-α, Activin B, and HB-EGF. These growth factors modulate downstream BMP4 signaling, the ERK cascade, and JNK/c-JUN. Several mechanisms, such as the Wnt/β-catenin signaling pathway, may inhibit and regulate eyelid fusion. Eyelid opening, on the other hand, is driven by the BMP/Smad signaling system. Several human genetic disorders result from dysregulation of the above molecular pathways. KEYWORDS: Embryology; epithelium; eyelid; genetics

PMID 26863902

2008

GPR48 regulates epithelial cell proliferation and migration by activating EGFR during eyelid development

Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4245-53. Epub 2008 May 16.

Jin C, Yin F, Lin M, Li H, Wang Z, Weng J, Liu M, Da Dong X, Qu J, Tu L.

School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, PR China.

Abstract PURPOSE: Eyelid development is a dynamic process involving cell proliferation, differentiation, and migration regulated by a number of growth factors and cytokines. Mice deficient in the orphan G protein-coupled receptor 48 (GPR48) showed an eye open at birth (EOB) phenotype. In this study, the authors attempted to clarify the role of GPR48 in eyelid development and the molecular mechanisms leading to the EOB phenotype.

METHODS: Phenotypic analysis of the eyelids of Gpr48(-/-) mice was carried out using histology and scanning electron microscopy. GPR48 expression pattern was determined using X-gal staining. In vitro scratch assay was used to determine cell motility defects in Gpr48(-)(/)(-) keratinocytes. The molecular mechanism underlying GPR48-mediated eyelid closure was explored using Western blot and immunostaining analyses. Expression levels of EGFR and its phosphorylated counterpart were examined in Gpr48(-/-) and wild-type keratinocytes and in eyelids.

RESULTS: GPR48 is highly expressed in the epithelium and apical mesenchymal cells of eyelids during embryonic development. Detailed analysis revealed that Gpr48(-/-) mice exhibited delayed leading-edge extension, reduced filopodia formation, and decreased rounded periderm cell formation around eyelid margins. Keratinocytes lacking GPR48 are defective in cell proliferation and migration with reduced F-actin staining. In addition, the phosphorylation of EGFR was dramatically decreased in cultured keratinocytes and developing eyelids in the absence of GPR48.

CONCLUSIONS: Inactivation of GPR48 induces the EOB phenotype by reducing epithelial cell proliferation and migration, indicating that GPR48 plays an essential role in eyelid development. Furthermore, GPR48 contributes to eyelid development through the regulation of the EGFR signaling pathway.

PMID 18487371 http://www.ncbi.nlm.nih.gov/pubmed/18487371

2005

HB-EGF promotes epithelial cell migration in eyelid development

Development. 2005 Oct;132(19):4317-26. Epub 2005 Sep 1.

Mine N, Iwamoto R, Mekada E.

Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan.

Abstract

Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of growth factors that binds to and activates the EGF receptor (EGFR) and ERBB4. Here, we show that HB-EGF-EGFR signaling is involved in eyelid development. HB-EGF expression is restricted to the tip of the leading edge of the migrating epithelium during eyelid closure in late gestation mouse embryos. Both HB-EGF null (HB(del/del)) and secretion-deficient (HB(uc/uc)) mutant embryos exhibited delayed eyelid closure, owing to slower leading edge extension and reduced actin bundle formation in migrating epithelial cells. No changes in cell proliferation were observed in these embryos. In addition, activation of EGFR and ERK was decreased in HB(del/del) eyelids. Crosses between HB(del/del) mice and waved 2 mice, a hypomorphic EGFR mutant strain, indicate that HB-EGF and EGFR interact genetically in eyelid closure. Together with our data showing that embryos treated with an EGFR-specific kinase inhibitor phenocopy HB(del/del) embryos, these data indicate that EGFR mediates HB-EGF-dependent eyelid closure. Finally, analysis of eyelid closure in TGFalpha-null mice and in HB-EGF and TGFalpha double null mice revealed that HB-EGF and TGFalpha contribute equally to and function synergistically in this process. These results indicate that soluble HB-EGF secreted from the tip of the leading edge activates the EGFR and ERK pathway, and that synergy with TGFalpha is required for leading edge extension in epithelial sheet migration during eyelid closure.

PMID 16141218 http://www.ncbi.nlm.nih.gov/pubmed/16141218

A dual role of FGF10 in proliferation and coordinated migration of epithelial leading edge cells during mouse eyelid development

Development. 2005 Jul;132(14):3217-30. Epub 2005 Jun 15.

Tao H, Shimizu M, Kusumoto R, Ono K, Noji S, Ohuchi H.

Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, 2-1 Minami-Jyosanjima, Tokushima 770-8506, Japan.

Abstract

The development of the eyelid requires coordinated cellular processes of proliferation, cell shape changes, migration and cell death. Mutant mice deficient in the fibroblast growth factor 10 (Fgf10) gene exhibit open-eyelids at birth. To elucidate the roles of FGF10 during eyelid formation, we examined the expression pattern of Fgf10 during eyelid formation and the phenotype of Fgf10-null eyelids in detail. Fgf10 is expressed by mesenchymal cells just beneath the protruding epidermal cells of the nascent eyelid. However, Fgf10-null epithelial cells running though the eyelid groove do not exhibit typical cuboid shape or sufficient proliferation. Furthermore, peridermal clumps are not maintained on the eyelid leading edge, and epithelial extension does not occur. At the cellular level, the accumulation of actin fibers is not observed in the mutant epithelial leading edge. The expression of activin/inhibin betaB (ActbetaB/Inhbb) and transforming growth factor alpha (Tgfa), previously reported to be crucial for eyelid development, is down-regulated in the mutant leading edge, while the onset of sonic hedgehog (Shh) expression is delayed on the mutant eyelid margin. Explant cultures of mouse eyelid primordia shows that the open-eyelid phenotype of the mutant is reduced by exogenous FGF10 protein, and that the expression of ActbetaB and Tgfa is ectopically induced in the thickened eyelid epithelium by the FGF10 protein. These results indicate a dual role of FGF10 in mouse eyelid development, for both proliferation and coordinated migration of eyelid epithelial cells by reorganization of the cytoskeleton, through the regulation of activin, TGFalpha and SHH signaling.

PMID: 15958512

1993

Eyelid development, fusion and subsequent reopening in the mouse

J Anat. 1993 Aug;183 ( Pt 1):121-9.

Findlater GS, McDougall RD, Kaufman MH.

Department of Anatomy, University Medical School, Edinburgh, UK. Abstract The process of eyelid development was studied in the mouse. The critical events occur between about 15.5 d postcoitum (p.c.) and 12 d after birth, and were studied by conventional histology and by scanning electron microscopy. At about 15.5 d p.c. the cornea of the eye is clearly visible with the primitive eyelids being represented by protruding ridges of epithelium at its periphery. Over the next 24 h, eyelid development proceeds to the stage when the cornea is completely covered by the fused eyelids. Periderm cells stream in to fill the gap between the developing eyelids. Their proliferative activity is such that they produce a cellular excrescence on the outer surface of the line of fusion of the eyelids. This excrescence had almost disappeared by about 17.5 d p.c. Keratinisation is first evident at this stage on the surface of the eyelids and passes continuously from one eyelid to the other. Evidence of epidermal differentiation is more clearly seen in the newborn, where a distinctive stratum granulosum now occupies about one third of its entire thickness. Within the subjacent dermis, hair follicles are differentiating. By about 5 d after birth, a thick layer of keratin extends without interruption across the junctional region. While a noticeable surface indentation overlies the latter, a similar depression is only seen on the conjunctival surface by about 10 d after birth. Keratinisation is also observed to extend in from the epidermal surface to involve the entire region between the 2 eyelids at about this time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 8270467

1982

Eyelid growth and fusion in fetal mice. A scanning electron microscope study

Anat Embryol (Berl). 1982;164(2):207-20.

Harris MJ, McLeod MJ.

Abstract During the last phase of mammalian morphogenesis, between days 14 and 16 of gestation in the mouse, the fetal eyelids grow across the eye and become tightly fused with each other. This paper describes the surface pattern of fetal eyelids, revealed by the scanning electron microscope, during normal eyelid growth and fusion in the ICR/MI stock of mice. Fusion proceeds from both inner and outer canthi and progresses toward the middle of the gap. The first changes in cell shape and distribution occur at the inner canthus. On day 14, a large clump of rounded cells appears on the inner surface of the inner canthus. A day later, two clumps of rounded cells are positioned to either side of, i.e. above and below, the inner canthus. As fusion progresses, the diminishing gap fills with a profusion of rounded cells that are extruded, flattened, and sloughed off from the area of completed fusion. The profusion of rounded surface cells during eyelid growth and fusion appears to be a major characteristic in which the eyelid fusion process differs both from permanent fusions, such as the fusion of the neural tube, lip or palate, and from other temporary fusions, such as fusion of the digits to each other or of the pinnae to the scalp.

PMID 7125235