ZFIN ID: ZDB-PUB-191102-11
Lysyl hydroxylase 3 is required for normal lens capsule formation and maintenance of lens epithelium integrity and fate
Taler, K., Weiss, O., Rotem, S., Rubinstein, A.M., Seritrakul, P., Gross, J.M., Inbal, A.
Date: 2019
Source: Developmental Biology   458(2): 177-188 (Journal)
Registered Authors: Gross, Jeffrey, Inbal, Adi, Seritrakul, Pawat
Keywords: Lens capsule, Lens epithelium, Lysyl hydroxylase 3, TGFβ, Zebrafish, plod3
MeSH Terms:
  • Actins/genetics
  • Actins/metabolism
  • Animals
  • Cataract/genetics
  • Cell Differentiation/physiology
  • Embryonic Development
  • Epithelial Cells/pathology
  • Epithelium/pathology
  • Glycosyltransferases/genetics*
  • Glycosyltransferases/metabolism
  • Lens Capsule, Crystalline/embryology*
  • Lens Capsule, Crystalline/metabolism*
  • Lens, Crystalline/embryology
  • Phenotype
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics*
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 31669351 Full text @ Dev. Biol.
Lens abnormalities are a major cause of reduced vision and blindness. One mechanism that can lead to reduced lens transparency, i.e. cataract, is abnormal behavior of lens epithelial cells (LECs), the precursors of the transparent lens fiber cells. Here we describe a zebrafish mutation causing the embryonic lens epithelium to generate cellular masses comprising partially differentiated lens fiber cells. We identify the mutant gene as plod3, which encodes for Lysyl hydroxylase 3 (Lh3), an enzyme essential for modification of collagens, including Collagen IV, a main component of the lens capsule. We show that plod3-deficient lenses have abnormal lens epithelium from an early developmental stage, as well as abnormal lens capsules. Subsequently, upregulation of TGFβ signaling takes place, which drives the formation of lens epithelial cellular masses. We identify a similar phenotype in Collagen IVα5-deficient embryos, suggesting a key role for the defective lens capsule in the pathogenesis. We propose that plod3 and col4a5 mutant zebrafish can serve as useful models for better understanding the biology of LECs during embryonic development and in formation of lens epithelium-derived cataract.