Receptor Tyrosine Kinase Signaling in Mammalian Eye Development.

Authors

Neoklis Makrides, Yihua Wu, Yelenia Almonte, Xin Zhang, Chenqi Tao

Published in

Developmental biology. Sep 19, 2026. Epub Sep 19, 2026.

Abstract

Receptor tyrosine kinase (RTK) signaling is a central mechanism by which local tissue interactions are translated into coordinated morphogenesis during eye development. The vertebrate eye provides a uniquely tractable system for studying this logic because it is assembled from neural epithelium, surface ectoderm, neural crest-derived mesenchyme, vascular endothelium, and specialized epithelial and endothelial derivatives across a prolonged developmental timeline. In this review, we synthesize how major RTK families, including FGF-FGFR, EGF-ErbB, PDGF-PDGFR, VEGF-VEGFR, Eph-ephrin, ANGPT-TEK/Tie2, IGF-INS receptors, and collagen-sensing DDRs, control optic cup formation, optic fissure closure, lens differentiation and architecture, corneal and anterior segment morphogenesis, retinal vascularization, Schlemm's canal development, and lacrimal gland branching. Rather than acting through pathway-specific outputs, these receptors repeatedly converge on shared MAPK/ERK, PI3K-AKT, PLCγ-PKC, SRC/FAK, and Rho-family cytoskeletal modules. Developmental specificity emerges from ligand geography, receptor dosage, co-receptor and extracellular matrix context, signal duration, receptor trafficking, mechanical state, and cross-talk with other signaling pathways. We also highlight how emerging single-cell, spatial, and multiomic atlases are shifting the field from static expression maps toward ligand-receptor source mapping and quantitative pathway-state inference. Finally, we connect developmental RTK mechanisms to congenital and pediatric eye disease. Together, these studies position the eye as a powerful model for understanding how reiterative RTK signaling builds complex organ form and informs therapeutic modulation, regenerative medicine, and disease mechanism.

PMID:
42762961
Bibliographic data and abstract were imported from PubMed on 20 Sep 2026.

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