title: Matrix metalloproteinase 14 in the zebrafish: an eye on retinal and retinotectal development.
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.
  
  
  CONCLUSIONS
  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.
authors: Research Group Neural Circuit Development and Regeneration, Department of Biology, Katholieke Universiteit Leuven (KU Leuven), Leuven, Belgium.
authors: Els
authors: E
authors: Janssens
authors: Djoere
authors: D
authors: Gaublomme
authors: Lies
authors: L
authors: De Groef
authors: Veerle M
authors: VM
authors: Darras
authors: Lut
authors: L
authors: Arckens
authors: Nathalie
authors: N
authors: Delorme
authors: Filip
authors: F
authors: Claes
authors: Inge
authors: I
authors: Van Hove
authors: Lieve
authors: L
authors: Moons
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000235:genetics* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008850:Microphthalmos / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D055495:Neurogenesis / Q000235:genetics; D009899:Optic Lobe, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011485:Protein Binding; D012160:Retina / Q000196:embryology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14