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Published on: March 2, 2022
Matrix metalloproteinase 14 in the zebrafish: an eye on retinal and retinotectal development
Els Janssens1, Djoere Gaublomme, Lies De Groef
1Research Group Neural Circuit Development and Regeneration, Department of Biology, Katholieke Universiteit Leuven (KU Leuven), Leuven, Belgium.
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.
Insights
Zebrafish Mmp14a is crucial for retinal development and the formation of visual system connections. Loss of Mmp14a function delays neurogenesis and impairs optic tectum innervation.
Area of Science:
- Developmental biology
- Neuroscience
- Molecular biology
Background:
- Matrix metalloproteinases (MMPs) are enzymes involved in extracellular matrix remodeling and signal transduction.
- While MMPs are known to influence retinotectal projection development, specific roles in retinal development are not fully understood.
Purpose of the Study:
- To investigate the role of zebrafish Mmp14a, a paralog of human MMP14, in retinal neurogenesis and retinotectal development.
Main Methods:
- Whole mount in situ hybridization and immunohistochemical staining for Mmp14a expression in zebrafish embryos.
- Analysis of Mmp14a loss-of-function mutants to assess effects on retinal development and optic tectum innervation.
- Investigation of the functional link between Mmp14a and Mmp2.
Main Results:
- Mmp14a is expressed in the developing zebrafish optic tectum, optic nerve, and retinal cells, including retinal ganglion cells (RGCs).
- Mmp14a loss-of-function causes delayed retinal neurogenesis, differentiation, and lamination, leading to microphthalmia and reduced RGC axon innervation of the optic tectum.
- Mmp14b does not significantly impact retinal neurogenesis or optic tectum innervation.
- A functional link between Mmp14a and Mmp2 in retinotectal development was identified.
Conclusions:
- Mmp14a plays a critical role in the development of the zebrafish visual system, including retinal development and retinotectal connections.
- Mmp14a activity is essential for proper cell cycle kinetics, neurogenesis, differentiation, and lamination in the retina.
