%0 Generic
%A Schlagheck, Christina Maria
%C Heidelberg
%D 2025
%F heidok:36901
%R 10.11588/heidok.00036901
%T Organoid-based studies on the fundamental rules of retinal tissue self-organization and patterning
%U https://archiv.ub.uni-heidelberg.de/volltextserver/36901/
%X The formation of an organ during development is a complex, highly regulated process that involves a variety of signals provided by the organismal context. In contrast, in culture, stem cells self-organize into 3D tissues, which recapitulate certain aspects of tissue architecture and cell composition seen in vivo. These organoids provide a valuable tool for analyzing tissue formation under controlled biochemical or biomechanical conditions.  In this study, I employed retinal organoids grown from blastula cells of medaka fish (Oryzias latipes), which recapitulate aspects of early retinal development but fail to undergo the characteristic morphogenesis of the retina to the double-layered cup-shape, nor form cells of the ciliary margin zone (CMZ). Using this system, I investigated how mechanical cues instruct retinal cell type specification in retinal organoids and explored the self-organization of retinal cells in different environments.  Specifically, I examined the effect of mechanically-induced tissue bending on CMZ formation in retinal organoids, revealing that artificial imposition of tissue shape alone was not sufficient to induce CMZ. However, spontaneous emergence of CMZ-tissue within retinal organoids that contain both retinal and non-retinal tissue suggests the importance of tissue boundaries for establishing the different retinal domains.  Further, I investigated the formation of the neural retina (NR) in the medaka organoids. I show that NR cell types differentiate and form clusters of recurring composition and arrangement. Contrasting with the stratified NR formed in the embryo, the cluster formation poses a striking alternative patterning of retinal cells, which is reminiscent of the compound eyes of insects. Supplementation of the organoid culture with Laminin enabled the establishment of NR cell layering.  The results presented in this thesis provide insight into basic patterning processes employed by medaka retinal cells in reduced environments. Considering these features of organoids in future studies may help to understand evolutionary transitions between different organ phenotypes across species.