<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Organoid assembloids modelling the role of serotonin during human cortical development"^^ . "The development of the human cortex involves the coordinated interplay between cell proliferation,\r\nmigration and differentiation. Serotonergic projections from the raphe nuclei were shown to reach the\r\ndeveloping cortex at early stages, prior to the main expansion period. Subsequently, serotonin has\r\nbeen linked to several aspects of corticogenesis, including proliferation. However, the lack of\r\nappropriate models impedes deepening our understanding of the role of serotonin in human\r\ncorticogenesis. In this context, human induced stem cell (hiPSC)-derived culture systems became of\r\ninterest as regionalized brain organoids have been shown to faithfully recapitulate certain aspects of\r\nhuman brain development.\r\nIn this thesis, hiPSC-derived 2D and 3D model systems were applied to decipher the effect of serotonin\r\non distinct cortical progenitor pools. Thus, apical progenitor cells (aPCs) were identified as recipients\r\nof serotonin. Specifically, activation of the serotonergic receptor 5-HT2C was required and sufficient to\r\ninduce proliferation. Secondly, a mitogenic effect of serotonin was also observed in basal progenitor\r\ncells (bPCs), a precursor type fundamental for human brain development, e.g. human-specific cortical\r\nexpansion. The increased proliferation was here mediated by the receptor 5-HT2A. Interestingly, no\r\nchange in proliferation behavior was observed in intermediate progenitors (IPs).\r\nTo closer resemble the interplay between serotonergic neurons and the developing cortex, cortical-\r\nraphe assembloids were established. Whereby, a new organoid model was developed mimicking the\r\nraphe nuclei. At early time points, raphe organoids (RO) were composed of progenitors exhibiting\r\nexpression of characteristic markers of serotonergic precursors including NKX2.2 and FOXA2. RO\r\nultimately generated serotonergic neurons marked by TPH2, VMAT2 and serotonin itself. Moreover,\r\nby applying the serotonin sensor sDarken the endogenous release of serotonin could be detected.\r\nBy fusing raphe with cortical organoids (CO) to assembloids, a model system was created representing\r\nthe influence of serotonergic innervation on human corticogenesis. Specifically, RO-derived\r\nserotonergic projections were observed in cortical structures and the utilization of sDarken in CO\r\ndemonstrated serotonergic innervation. Finally, ventricular zones showed elevated proliferation in the\r\npresence of serotonergic projections.\r\nTaken together, hiPSC-derived organoids displayed distinct mitogenic effects of exogenous serotonin\r\non different progenitor populations, namely aPCs and bPCs but not IPs. Moreover, the generated\r\nassembloid proved valuable by displaying endogenous serotonergic innervation and recapitulating the\r\nmitogenic effect of serotonin. Thus, RO-CO assembloids enable further decipherment of the\r\nserotonergic role during human corticogenesis and open the possibility to study associated diseases,\r\nincluding autism spectrum disorder."^^ . "2023" . . . . . . . "Marco Torben"^^ . "Siekmann"^^ . "Marco Torben Siekmann"^^ . . . . . . "Organoid assembloids modelling the role of serotonin during human cortical development (PDF)"^^ . . . "Dissertation_Siekmann.pdf"^^ . . . "Organoid assembloids modelling the role of serotonin during human cortical development (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Organoid assembloids modelling the role of serotonin during human cortical development (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Organoid assembloids modelling the role of serotonin during human cortical development (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Organoid assembloids modelling the role of serotonin during human cortical development (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Organoid assembloids modelling the role of serotonin during human cortical development (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #33701 \n\nOrganoid assembloids modelling the role of serotonin during human cortical development\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .