The roles of mab21l2 in development of the eye




Gath, Natalie Nicole

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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 [superscript au10] mutants possess ocular defects resembling those in humans with MAB21L2 mutations, providing an excellent model to characterize mab21l2 functions during eye development. mab21l2 [superscript -/-] 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 [superscript -/-] 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 [superscript -/-] mutant corneas were disorganized, possessed an increased number of cells, some of which proliferated ectopically, and failed to differentiate the corneal stroma. Human mutant MAB21L2 [superscript R51C] and MAB21L2 [superscript R51H] mRNAs possessed dominant negative function, inducing colobomas in wild type fish. Yeast-2-hybrid assays provided potential binding partners for the function of mab21l2, including transcription factors and actin/myosin related proteins. 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. mab21l2 protein function may involve transcriptional regulation or control of cell shape and movement.


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