Integumentary System - Eyelid Development

Introduction

The eyelids represent integumentary specialisations that cover and protect the eye cornea.

Note that some species, such as rodents, are born with closed eyelids.

The palpebral commissure (canthus) is located at the corner of the eye where the upper and lower eyelids meet.

Human embryo head showing eyelid development (Stage 22, Week 8)

Embryo head cross-section.

Some Recent Findings

Molecular biology and genetics of embryonic eyelid development "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." Glucocorticoid receptor antagonizes EGFR function to regulate eyelid development "Eyelid formation constitutes a useful model to study epithelial development, as it requires coordinated regulation of keratinocyte proliferation, apoptosis and migration. ...Our data demonstrate that glucocorticoid receptor (GR) deficiency results in delayed and impaired eyelid closure, as illustrated by increased keratinocyte proliferation and apoptosis along with impaired differentiation in GR(-/-) eyelid epithelial cells."

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Eyelid Embryology | Eyelid Development

Older papers

These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. HB-EGF promotes epithelial cell migration in eyelid development "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. ...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." Eyelid fusion and epithelial differentiation at the ocular surface during mouse embryonic development "Eyelid fusion is a critical period for differentiation of the ocular surface ectoderm into the epithelia of the conjunctiva, cornea, and eyelid skin. The conjunctival epithelium differentiates before the corneal epithelium, which in turn differentiates before the eyelid epidermis."

Human Eyelid Timeline

Human Embryonic Eyelid Timeline

Carnegie Stage	Event
10	optic primordia appear
13	By the end of the fourth week the optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode.
14	(about 32 days) the lens placode is indented by the lens pit.
15	(about 33 days) the lens pit is closed. The lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface.
16	(37 days) Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it.
17 - 19	grooves deepen, eyelid folds develop, first below, and then above, the eye.
19 - 22	eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19.
20	the inner canthus is established.
23	closure of the eyelids is complete (Note - shown as still open in some Kyoto embryo).
	Data - from Kyoto embryos with Carnegie staging.   Links: eyelid

The images below link to virtual slides of the human developing eye at Carnegie stage 22. Click on the image to open or select specific regions from the regions of interest links.

Stage 22 - Eye and Nose  ‎‎Mobile | Desktop | Original Stage 22 | Embryo Slides

Stage 22 - Eye  ‎‎Mobile | Desktop | Original Stage 22 | Embryo Slides

Virtual Slide - Regions of Interest Eye Overview Lens and Cornea Cornea and Anterior Chamber Links: Embryo Virtual Slides

Adult Anatomy

The palpebral commissure (canthus) is located at the corner of the eye where the upper and lower eyelids meet.

Molecular

See recent article on molecular biology and genetics of embryonic eyelid development.

• cell migration - FGF10, TGF-α, Activin B, and HB-EGF modulate downstream BMP4 signaling, the ERK cascade, and JNK/c-JUN.
• Wnt/β-catenin signaling pathway - may inhibit and regulate eyelid fusion.

Abnormalities

Congenital upper eyelid ectopic cilia

References

Reviews

Zieske JD. (2004). Corneal development associated with eyelid opening. Int. J. Dev. Biol. , 48, 903-11. PMID: 15558481 DOI.

Hamming N. (1983). Anatomy and embryology of the eyelids: a review with special reference to the development of divided nevi. Pediatr Dermatol , 1, 51-8. PMID: 6387662

Articles

Meng Q, Mongan M, Carreira V, Kurita H, Liu CY, Kao WW & Xia Y. (2014). Eyelid closure in embryogenesis is required for ocular adnexa development. Invest. Ophthalmol. Vis. Sci. , 55, 7652-61. PMID: 25377219 DOI.

Du X, Tabeta K, Hoebe K, Liu H, Mann N, Mudd S, Crozat K, Sovath S, Gong X & Beutler B. (2004). Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice. Genetics , 166, 331-40. PMID: 15020428

Findlater GS, McDougall RD & Kaufman MH. (1993). Eyelid development, fusion and subsequent reopening in the mouse. J. Anat. , 183 ( Pt 1), 121-9. PMID: 8270467

Harris MJ & McLeod MJ. (1982). Eyelid growth and fusion in fetal mice. A scanning electron microscope study. Anat. Embryol. , 164, 207-20. PMID: 7125235

Search PubMed

Search Pubmed: Eyelid Development

Additional Images

Historic

Historic Disclaimer - information about historic embryology pages

Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Gray H. Anatomy of the human body. (1918) Philadelphia: Lea & Febiger.

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  892 Front of left eye with eyelids separated to show medial canthus

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  893 Structure of the Eyelids

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  894 The tarsi and their ligaments

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  895 The Tarsal Glands

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  896 The Lacrimal Gland

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  897 Structures of the Lacrimal Gland

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• Histology - Adult Eyelid

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Cite this page: Hill, M.A. (2024, April 19) Embryology Integumentary System - Eyelid Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Eyelid_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G