Natalie Gath1,2, Jeffrey M Gross1,2. 1. Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas. 2. Departments of Ophthalmology and Developmental Biology, Louis J. Fox Center for Vision Restoration, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Abstract
BACKGROUND: Mutations in MAB21L2 result in severe ocular defects including microphthalmia, anophthalmia, coloboma, microcornea, and cataracts. The molecular and cellular underpinnings of these defects are unknown, as is the normal cellular function of MAB21L2. Zebrafish mab21l2 au10 mutants possess ocular defects resembling those in humans with MAB21L2 mutations, providing an excellent model to characterize mab21l2 functions during eye development. RESULTS: mab21l2 -/- mutants possessed a host of ocular defects including microphthalmia and colobomas as well as small, disorganized lenses and cornea dysgenesis. Decreased proliferation, increased cell death, and defects in marker gene expression were detected in the lens. Cell death in the optic stalk was elevated in mab21l2 -/- mutants and the basement membrane between the edges of the choroid fissure failed to break down. Neuronal differentiation in the retina was normal, however. mab21l2 -/- mutant corneas were disorganized, possessed an increased number of cells, some of which proliferated ectopically, and failed to differentiate the corneal stroma. CONCLUSIONS: mab21l2 function is required for morphogenesis and cell survival in the lens and optic cup, and basement membrane breakdown in the choroid fissure. mab21l2 function also regulates proliferation in the lens and cornea; in its absence, the lens is small and mispatterned, and corneal morphogenesis and patterning are also disrupted.
BACKGROUND: Mutations in MAB21L2 result in severe ocular defects including microphthalmia, anophthalmia, coloboma, microcornea, and cataracts. The molecular and cellular underpinnings of these defects are unknown, as is the normal cellular function of MAB21L2. Zebrafishmab21l2 au10 mutants possess ocular defects resembling those in humans with MAB21L2 mutations, providing an excellent model to characterize mab21l2 functions during eye development. RESULTS:mab21l2 -/- mutants possessed a host of ocular defects including microphthalmia and colobomas as well as small, disorganized lenses and cornea dysgenesis. Decreased proliferation, increased cell death, and defects in marker gene expression were detected in the lens. Cell death in the optic stalk was elevated in mab21l2 -/- mutants and the basement membrane between the edges of the choroid fissure failed to break down. Neuronal differentiation in the retina was normal, however. mab21l2 -/- mutant corneas were disorganized, possessed an increased number of cells, some of which proliferated ectopically, and failed to differentiate the corneal stroma. CONCLUSIONS:mab21l2 function is required for morphogenesis and cell survival in the lens and optic cup, and basement membrane breakdown in the choroid fissure. mab21l2 function also regulates proliferation in the lens and cornea; in its absence, the lens is small and mispatterned, and corneal morphogenesis and patterning are also disrupted.
Authors: Andrea James; Chanjae Lee; Andre M Williams; Krista Angileri; Kira L Lathrop; Jeffrey M Gross Journal: Dev Biol Date: 2016-09-12 Impact factor: 3.582
Authors: Julian Morcillo; Juan Ramon Martínez-Morales; Françoise Trousse; Yasmin Fermin; Jane C Sowden; Paola Bovolenta Journal: Development Date: 2006-07-19 Impact factor: 6.868
Authors: M Mariani; D Baldessari; S Francisconi; L Viggiano; M Rocchi; V Zappavigna; N Malgaretti; G G Consalez Journal: Hum Mol Genet Date: 1999-12 Impact factor: 6.150
Authors: Sarah E Seese; Linda M Reis; Brett Deml; Christopher Griffith; Adi Reich; Robyn V Jamieson; Elena V Semina Journal: Hum Mutat Date: 2021-05-24 Impact factor: 4.878