Integumentary System - Eyelid Development

From Embryology


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.
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Some Recent Findings

  • Molecular biology and genetics of embryonic eyelid development[1] "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[2] "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."
  • HB-EGF promotes epithelial cell migration in eyelid development[3] "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[4] "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."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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Search term: Eyelid Embryology

Human Eyelid Timeline

The following data is from a study of human embryonic carnegie stages.[5]
  • Stage 10 optic primordia appear.
  • Stage 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.
  • Stage 14 - (about 32 days) the lens placode is indented by the lens pit.
  • Stage 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.
  • Stage 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.
  • Stages 17 - 19 - these grooves deepen, eyelid folds develop, first below, and then above, the eye.
  • Stages 19 - 22 - the 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.
  • Stage 20 - the inner canthus is established.
  • Stage 23 - closure of the eyelids is complete (Note - shown as still open in the Kyoto embryo).
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

Stage 22 image 008.jpg

 ‎‎Mobile | Desktop | Original

Stage 22 | Embryo Slides
Stage 22 - Eye

Stage 22 image 008-eye.jpg

 ‎‎Mobile | Desktop | Original

Stage 22 | Embryo Slides

Virtual Slide - Regions of Interest

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.


See recent article on molecular biology and genetics of embryonic eyelid development.[1]

  • 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.


Congenital upper eyelid ectopic cilia


  1. 1.0 1.1
  2. Ana Sanchis, Pilar Bayo, Lisa M Sevilla, Paloma Pérez Glucocorticoid receptor antagonizes EGFR function to regulate eyelid development. Int. J. Dev. Biol.: 2010, 54(10);1473-80 PubMed 21136383
  3. Naoki Mine, Ryo Iwamoto, Eisuke Mekada HB-EGF promotes epithelial cell migration in eyelid development. Development: 2005, 132(19);4317-26 PubMed 16141218
  4. Hui Zhang, Makiko Hara, Keisuke Seki, Ken Fukuda, Teruo Nishida Eyelid fusion and epithelial differentiation at the ocular surface during mouse embryonic development. Jpn. J. Ophthalmol.: 2004, 49(3);195-204 PubMed 15944823
  5. A A Pearson The development of the eyelids. Part I. External features. J. Anat.: 1980, 130(Pt 1);33-42 PubMed 7364662


James D Zieske Corneal development associated with eyelid opening. Int. J. Dev. Biol.: 2004, 48(8-9);903-11 PubMed 15558481

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


Qinghang Meng, Maureen Mongan, Vinicius Carreira, Hisaka Kurita, Chia-Yang Liu, Winston Kao, Ying Xia Eyelid closure in embryogenesis is required for ocular adnexa development. Invest. Ophthalmol. Vis. Sci.: 2014; PubMed 25377219

Xin Du, Koichi Tabeta, Kasper Hoebe, Haiquan Liu, Navjiwan Mann, Suzanne Mudd, Karine Crozat, Sosathya Sovath, Xiaohua Gong, Bruce Beutler Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice. Genetics: 2004, 166(1);331-40 PubMed 15020428

G S Findlater, R D McDougall, M H Kaufman Eyelid development, fusion and subsequent reopening in the mouse. J. Anat.: 1993, 183 ( Pt 1);121-9 PubMed 8270467

M J Harris, M J McLeod Eyelid growth and fusion in fetal mice. A scanning electron microscope study. Anat. Embryol.: 1982, 164(2);207-20 PubMed 7125235

Search PubMed

Search Pubmed: Eyelid Development

Additional Images


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

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Cite this page: Hill, M.A. (2018, December 9) Embryology Integumentary System - Eyelid Development. Retrieved from

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© Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G