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K.J. Wahlin, R. Adler; Dynamics of Synaptic Assembly in Developing Chick Embryo Photoreceptors . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4182.
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© ARVO (1962-2015); The Authors (2016-present)
The lack of synapse formation between graft and host tissues remains a major obstacle for cell replacement therapy aimed at treating blinding retinal degenerations. Overcoming this limitation would require inducing transplanted cells and their adult host retina to recapitulate the events underlying synaptogenesis in the embryo. The purpose of this study was to elucidate some aspects of these phenomena in the developing chick retina.
A developmental series of embryonic retinas were either lysed for RNA isolation and cDNA synthesis, or fixed for histological sectioning. Semi–quantitative PCR, immunocytochemistry (ICC), in situ hybridization (ISH) and confocal microscopy were used to investigate expression patterns of pre–synaptic, post–synaptic and cell adhesion molecules. Globally amplified cDNA from photoreceptor and inner retinal layers, isolated by laser capture micro–dissection (LCM), were also analyzed by PCR to delineate differences in expression between retinal layers.
Photoreceptor terminals become organized at a molecular level during a restricted, 3–day long period, when synthesis, transport and assembly of synaptic components occur in a defined sequence. An early phase of synthesis of synaptic precursors (i.e.CSP–1, PSD–95, SV2) appeared initially restricted to inner segments (IS), but by ED16 transport packets of building blocks were seen migrating along the soma, towards synaptic terminals. Concomitant decreases in the IS suggested that synthesis was downregulated at that time. Pre–synaptic components became assembled into mature synaptic structures by ED18, when they showed piccolo(+) synaptic ribbons. These pre–synaptic events correlated temporally with the differentiation of post–synaptic structures, which invaginate into PhR terminals and express GluR4 in the distal aspect of their dendrites.
Our results suggest that synapse formation between transplanted cells and an adult host would likely require the synthesis, transport and assembly of a large number of building blocks, which should be temporally and spatially coordinated in pre– and post–synaptic cells.
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