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Melanie Samuel, Courtney A Burger, Anna Casasent, Jonathan Alevy, Danye Jiang, Nicholas Albrecht, Justine Liang; LKB1 regulates cone driven laminar stratification in the outer retina.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6041.
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© ARVO (1962-2015); The Authors (2016-present)
Synapses in the outer retina are responsible for the initial stages of visual processing. These laminated connections form the outer plexiform layer (OPL) during the first postnatal week, but little is known about the cellular and molecular factors that drive OPL emergence and synapse specificity.
To identify factors that drive synapse formation in the outer retina, we focus on the serine/threonine kinase LKB1. We use gain and loss of function approaches to manipulate LKB1 in retina neurons generally and in each neuron type that connects in the OPL specifically: rods, cones, bipolar cells, and horizontal cells. We use immunohistochemistry, nanoscopic STORM imaging, and single cell reconstruction to test which neurons drive OPL emergence and assess the cell specific role of LKB1 in these events.
We show that the serine/threonine kinase LKB1 is required for the emergence and organization of outer retina synapses. Deletion of LKB1 results in defective emergence of the OPL, characterized by disordered plexiform patches and a delay in OPL segregation. These events coincide with defects in cone terminal localization and were accompanied by delays in cone maturation and axon terminal extension, resulting in reduced cone axon length. Postsynaptic horizontal cell refinement was coordinately delayed. Cell specific deletion of LKB1 in horizontal cells or rods did not induce similar defects in OPL formation or horizontal cell refinement, suggesting that cones are the primary driver of synapse formation in the outer retina.
Together, these data implicate LKB1 as a central regulator of synapse formation in the outer retina and suggest that cone maturation instructs the timing and location of connectivity in the OPL.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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