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Peer-reviewedCC BY-NC 4.0Cells, Tissues, Organs

A Descriptive Study of Early Eyelid Morphogenesis in a Large-Scale Human Embryo Collection

  1. 1Department of Plastic and Reconstructive Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
  2. 2Congenital Anomaly Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
  3. 3Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan

Abstract

Introduction: Human eyelid development begins during the embryonic period. Although the general outline of early eyelid development has been described, many structures and developmental phenomena remain insufficiently investigated or controversial mainly due to the scarcity of human fetal specimens. The purpose of this study is to clarify these unresolved issues and to determine the precise developmental timing of each eyelid structure.

Methods: Fifty-six embryos (Carnegie stage [CS] 18–23) and six fetuses (early 9th week of development) from the Kyoto Collection were included in this study. The anatomical structures of the eyelid were observed using serial histological sections and external photographs, and the findings were described according to each developmental stage.

Results: This study showed that medial and lateral canthi formed between CS19 and CS21. Mesenchymal condensations corresponding to the prospective upper and lower eyelid retractor regions were first observed at CS18 and acquired a sheet-like configuration by the 9th week of development. Mesenchymal condensation at the future location of the medial palpebral ligament was first observed at CS20. The orbicularis oculi muscle primordium emerged at the 9th week. Eyelid fusion initiated on the nasal side at CS22. It then progressed from both the nasal and temporal sides toward the center, until completion at the 9th week. The lacrimal canaliculi first appeared at CS19.

Conclusion: Using the rich specimens of the Kyoto Collection, we newly identified the developmental timing of the prospective lower eyelid retractor complex and medial palpebral ligament regions, as well as the initiation of eyelid fusion on the nasal side. Furthermore, we established a detailed timeline of early human eyelid morphogenesis. Our findings may guide future research on human eyelid development, anatomy, and the mechanisms underlying congenital eyelid disorders.

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BibTeX
@article{kumakiri2026descriptive,
  title = {{A Descriptive Study of Early Eyelid Morphogenesis in a Large-Scale Human Embryo Collection}},
  author = {Masanori Kumakiri and Motoki Katsube and Natsuko Utsunomiya and Naoki Morimoto and Shigehito Yamada},
  journal = {Cells, Tissues, Organs},
  year = {2026},
  month = aug,
  doi = {10.1159/cto/acbag004},
  url = {https://doi.org/10.1159/cto/acbag004},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - A Descriptive Study of Early Eyelid Morphogenesis in a Large-Scale Human Embryo Collection
AU  - Masanori Kumakiri
AU  - Motoki Katsube
AU  - Natsuko Utsunomiya
AU  - Naoki Morimoto
AU  - Shigehito Yamada
PY  - 2026
DA  - 2026/08/31
JO  - Cells, Tissues, Organs
DO  - 10.1159/cto/acbag004
UR  - https://doi.org/10.1159/cto/acbag004
AB  - Introduction: Human eyelid development begins during the embryonic period. Although the general outline of early eyelid development has been described, many structures and developmental phenomena remain insufficiently investigated or controversial mainly due to the scarcity of human fetal specimens. The purpose of this study is to clarify these unresolved issues and to determine the precise developmental timing of each eyelid structure.  Methods: Fifty-six embryos (Carnegie stage [CS] 18–23) and six fetuses (early 9th week of development) from the Kyoto Collection were included in this study. The anatomical structures of the eyelid were observed using serial histological sections and external photographs, and the findings were described according to each developmental stage.  Results: This study showed that medial and lateral canthi formed between CS19 and CS21. Mesenchymal condensations corresponding to the prospective upper and lower eyelid retractor regions were first observed at CS18 and acquired a sheet-like configuration by the 9th week of development. Mesenchymal condensation at the future location of the medial palpebral ligament was first observed at CS20. The orbicularis oculi muscle primordium emerged at the 9th week. Eyelid fusion initiated on the nasal side at CS22. It then progressed from both the nasal and temporal sides toward the center, until completion at the 9th week. The lacrimal canaliculi first appeared at CS19.  Conclusion: Using the rich specimens of the Kyoto Collection, we newly identified the developmental timing of the prospective lower eyelid retractor complex and medial palpebral ligament regions, as well as the initiation of eyelid fusion on the nasal side. Furthermore, we established a detailed timeline of early human eyelid morphogenesis. Our findings may guide future research on human eyelid development, anatomy, and the mechanisms underlying congenital eyelid disorders.
SN  - 1422-6405
SN  - 1422-6421
ER  -