Integumentary System - Eyelid Development

From Embryology
Embryology - 23 Jun 2024    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)


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.
Integumentary Links: integumentary | Lecture | hair | tooth | nail | integumentary gland | mammary gland | vernix caseosa | melanocyte | touch | Eyelid | outer ear | Histology | integumentary abnormalities | Category:Integumentary
Hair Links  
Hair Links: Overview | Lanugo | Neonatal | Vellus | Terminal | Hair Follicle | Follicle Phases | Stem Cells | Molecular | Pattern | Puberty | Histology | Hair Colour | Arrector Pili Muscle | Hair Loss | Integumentary
Touch Links  
Touch Links: Touch Receptors | Touch Pathway | Pacinian Corpuscle | Meissner's Corpuscle | Merkel Cell | Sensory Modalities | Neural Crest Development | Neural System Development | Student project | Integumentary | Sensory System
Historic Embryology - Integumentary  
1906 Papillary ridges | 1910 Manual of Human Embryology | 1914 Integumentary | 1923 Head Subcutaneous Plexus | 1921 Text-Book of Embryology | 1924 Developmental Anatomy | 1941 Skin Sensory | Historic Disclaimer
Vision Links: vision | lens | retina | placode | extraocular muscle | cornea | eyelid | lacrima gland | vision abnormalities | Student project 1 | Student project 2 | Category:Vision | sensory
Historic Embryology - Vision 
Historic Embryology: 1906 Eye Embryology | 1907 Development Atlas | 1912 Eye Development | 1912 Nasolacrimal Duct | 1917 Extraocular Muscle | 1918 Grays Anatomy | 1921 Eye Development | 1922 Optic Primordia | 1925 Eyeball and optic nerve | 1925 Iris | 1927 Oculomotor | 1928 Human Retina | 1928 Retina | 1928 Hyaloid Canal | Historic Disclaimer

Some Recent Findings

  • Review - Embryologic and Fetal Development of the Human Eyelid[1] "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."
  • Molecular biology and genetics of embryonic eyelid development[2] "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."
More recent papers  
Mark Hill.jpg
PubMed logo.gif

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 | meibomian gland |Cryptophthalmia

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.

  • Glucocorticoid receptor antagonizes EGFR function to regulate eyelid development[3] "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[4] "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[5] "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.[6]   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

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.[2]

  • 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.


 ICD-11 LA14.0 Structural developmental anomalies of eyelids

LA14.00 Palpebral cleft or coloboma

LA14.01 Cryptophthalmia - isolated cryptophtalmia is a congenital abnormality in which the eyelids are absent and skin covers the ocular bulb, which is often microphthalmic.

LA14.02 Congenital entropion - the eyelid (usually the lower lid) folds inward. It is very uncomfortable, as the eyelashes constantly rub against the cornea and irritate it. Entropion is usually caused by genetic factors and very rarely it may be congenital when an extra fold of skin grows with the lower eyelid (epiblepharon).

LA14.03 Congenital ectropion - the lower eyelid turns outwards. It is one of the notable aspects of newborns exhibiting congenital Harlequin-type ichthyosis, but ectropion can occur due to any weakening of tissue of the lower eyelid.

LA14.04 Congenital ptosis - Congenital ptosis is characterised by superior eyelid drop present at birth.

LA14.05 Congenital eyelid retraction

LA14.06 Epibulbar choristoma

LA14.07 Ankyloblepharon filiforme adnatum - Isolated ankyloblepharon filiforme adnatum is characterised by the presence of single or multiple thin bands of connective tissue between the upper and lower eyelids, preventing full opening of the eye.


  1. Tawfik HA, Abdulhafez MH, Fouad YA & Dutton JJ. (2016). Embryologic and Fetal Development of the Human Eyelid. Ophthalmic Plast Reconstr Surg , 32, 407-414. PMID: 27124372 DOI.
  2. 2.0 2.1 Rubinstein TJ, Weber AC & Traboulsi EI. (2016). Molecular biology and genetics of embryonic eyelid development. Ophthalmic Genet. , 37, 252-9. PMID: 26863902 DOI.
  3. Sanchis A, Bayo P, Sevilla LM & Pérez P. (2010). Glucocorticoid receptor antagonizes EGFR function to regulate eyelid development. Int. J. Dev. Biol. , 54, 1473-80. PMID: 21136383 DOI.
  4. Mine N, Iwamoto R & Mekada E. (2005). HB-EGF promotes epithelial cell migration in eyelid development. Development , 132, 4317-26. PMID: 16141218 DOI.
  5. Zhang H, Hara M, Seki K, Fukuda K & Nishida T. (2005). Eyelid fusion and epithelial differentiation at the ocular surface during mouse embryonic development. Jpn. J. Ophthalmol. , 49, 195-204. PMID: 15944823 DOI.
  6. Pearson AA. (1980). The development of the eyelids. Part I. External features. J. Anat. , 130, 33-42. PMID: 7364662


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


Dong F, Call M, Xia Y & Kao WW. (2017). Role of EGF receptor signaling on morphogenesis of eyelid and meibomian glands. Exp. Eye Res. , 163, 58-63. PMID: 28950938 DOI.

Wang J, Call M, Mongan M, Kao WW & Xia Y. (2017). Meibomian gland morphogenesis requires developmental eyelid closure and lid fusion. Ocul Surf , 15, 704-712. PMID: 28284825 DOI.

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 Disclaimer - information about historic embryology pages 
Mark Hill.jpg
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.

Addison WHF. and How HW. The development of the eyelids of the albino rat, until the completion of disjunction. (1921) Amer. J Anat. 29: 1-32.

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

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, June 23) Embryology Integumentary System - Eyelid Development. Retrieved from

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