PRE2023-CREACION DE ORGANOIDES PARA EL ESTUDIO DEL DESARROLLO NORMAL Y PATOLOGICO DE LA MEDULA ESPINAL HUMANA-PID2022-139609NB-100

Human neural development occurs mainly in embryonic and foetal stages, and generates tremendously diverse neural cell types that constitute the human nervous system. Therefore, studies on human neurodevelopment have been limited due to the little access to human embryonic tissues. Today, neural organoids derived from human pluripotent stem cells not only recapitulate major developmental processes during morphogenesis and neurogenesis, but also exhibit human-specific features, thus providing an unprecedented opportunity to study human neurodevelopment in health and disease. This research proposal aims to (1) develop and validate human Spinal Cord (SC) organoids, with specific features of anterior and posterior SC regions, and to validate these biomodels to understand the basic principles in the acquisition of shape, size and cell diversity of the human SC. In particular, we propose to exploit these technological developments to understand (2) the collective tissue dynamics required for building the secondary neural tube and the possible accidents in the process of de novo lumen formation that might result in Spina Bifida Oculta, and (3) the signalling events and cell responses generating cell diversity in the early developing human SC. This research proposal is strongly founded in our expertise on the studies of the early patterning events and the signalling cascades at play during spinal cord development, that have provided the necessary foundations to make organoid research.