ZFIN ID: ZDB-PUB-160625-6
Loss of laminin alpha 1 results in multiple structural defects and divergent effects on adhesion during vertebrate optic cup morphogenesis
Bryan, C.D., Chien, C.B., Kwan, K.M.
Date: 2016
Source: Developmental Biology   416(2): 324-37 (Journal)
Registered Authors: Chien, Chi-Bin, Kwan, Kristen
Keywords: adhesion, cell polarity, eye morphogenesis, laminin, lens, retina
MeSH Terms:
  • Animals
  • Cell Movement
  • Cell Polarity
  • Extracellular Matrix/physiology
  • Eye Proteins/genetics
  • Eye Proteins/physiology*
  • Focal Adhesions
  • Laminin/deficiency
  • Laminin/genetics
  • Laminin/physiology*
  • Lens, Crystalline/embryology*
  • Luminescent Proteins/analysis
  • Luminescent Proteins/genetics
  • Microscopy, Confocal
  • Organogenesis
  • Retina/cytology
  • Retina/embryology*
  • Retinal Ganglion Cells/cytology
  • Retinal Pigment Epithelium/cytology
  • Retinal Pigment Epithelium/embryology
  • Time-Lapse Imaging
  • Zebrafish/embryology*
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 27339294 Full text @ Dev. Biol.
The vertebrate eye forms via a complex set of morphogenetic events. The optic vesicle evaginates and undergoes transformative shape changes to form the optic cup, in which neural retina and retinal pigmented epithelium enwrap the lens. It has long been known that a complex, glycoprotein-rich extracellular matrix layer surrounds the developing optic cup throughout the process, yet the functions of the matrix and its specific molecular components have remained unclear. Previous work established a role for laminin extracellular matrix in particular steps of eye development, including optic vesicle evagination, lens differentiation, and retinal ganglion cell polarization, yet it is unknown what role laminin might play in the early process of optic cup formation subsequent to the initial step of optic vesicle evagination. Here, we use the zebrafish lama1 mutant (lama1(UW1)) to determine the function of laminin during optic cup morphogenesis. Using live imaging, we find, surprisingly, that loss of laminin leads to divergent effects on focal adhesion assembly in a spatiotemporally-specific manner, and that laminin is required for multiple steps of optic cup morphogenesis, including optic stalk constriction, invagination, and formation of a spherical lens. Laminin is not required for single cell behaviors and changes in cell shape. Rather, in lama1(UW1) mutants, loss of epithelial polarity and altered adhesion lead to defective tissue architecture and formation of a disorganized retina. These results demonstrate that the laminin extracellular matrix plays multiple critical roles regulating adhesion and polarity to establish and maintain tissue structure during optic cup morphogenesis.