PUBLICATION

Matrix metalloproteinase 14 in the zebrafish: an eye on retinal and retinotectal development

Authors
Janssens, E., Gaublomme, D., De Groef, L., Darras, V.M., Arckens, L., Delorme, N., Claes, F., Van Hove, I., and Moons, L.
ID
ZDB-PUB-130125-14
Date
2013
Source
PLoS One   8(1): e52915 (Journal)
Registered Authors
Darras, Veerle
Keywords
Embryos, Eyes, Retina, Retinal ganglion cells, Zebrafish, Axons, Neurogenesis, Immunostaining
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism*
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • Gene Knockdown Techniques
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Isoenzymes/genetics
  • Isoenzymes/metabolism
  • Matrix Metalloproteinase 14/genetics*
  • Matrix Metalloproteinase 14/metabolism
  • Matrix Metalloproteinase 2/genetics
  • Matrix Metalloproteinase 2/metabolism
  • Microphthalmos/embryology
  • Microphthalmos/genetics
  • Microphthalmos/metabolism
  • Microscopy, Confocal
  • Neurogenesis/genetics
  • Optic Lobe, Nonmammalian/cytology
  • Optic Lobe, Nonmammalian/embryology
  • Optic Lobe, Nonmammalian/metabolism
  • Protein Binding
  • Retina/embryology
  • Retina/metabolism
  • Retinal Ganglion Cells/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
23326364 Full text @ PLoS One
Abstract

Background

Matrix metalloproteinases (MMPs) are members of the metzincin superfamily of proteinases that cleave structural elements of the extracellular matrix and many molecules involved in signal transduction. Although there is evidence that MMPs promote the proper development of retinotectal projections, the nature and working mechanisms of specific MMPs in retinal development remain to be elucidated. Here, we report a role for zebrafish Mmp14a, one of the two zebrafish paralogs of human MMP14, in retinal neurogenesis and retinotectal development.

Results

Whole mount in situ hybridization and immunohistochemical stainings for Mmp14a in developing zebrafish embryos reveal expression in the optic tectum, in the optic nerve and in defined retinal cell populations, including retinal ganglion cells (RGCs). Furthermore, Mmp14a loss-of-function results in perturbed retinoblast cell cycle kinetics and consequently, in a delayed retinal neurogenesis, differentiation and lamination. These Mmp14a-dependent retinal defects lead to microphthalmia and a significantly reduced innervation of the optic tectum (OT) by RGC axons. Mmp14b, on the contrary, does not appear to alter retinal neurogenesis or OT innervation. As mammalian MMP14 is known to act as an efficient MMP2-activator, we also explored and found a functional link and a possible co-involvement of Mmp2 and Mmp14a in zebrafish retinotectal development.

Conclusion

Both the Mmp14a expression in the developing visual system and the Mmp14a loss-of-function phenotype illustrate a critical role for Mmp14a activity in retinal and retinotectal development.

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