Descripción del proyecto
Dilucidar la estratificación neuronal en el ojo de los vertebrados
Muchas partes del sistema nervioso central se caracterizan por una estructura neuronal en capas, que facilita la transmisión de información. Sin embargo, todavía no comprendemos en detalle el mecanismo subyacente a nivel celular y tisular ni los principios que garantizan una estratificación neuronal correcta durante el desarrollo. El proyecto financiado con fondos europeos makingtheretina está investigando la emergencia de la estratificación neuronal en la retina de los vertebrados. Los investigadores utilizarán el pez cebra y organoides humanos para estudiar la migración de diferentes neuronas retinales durante el desarrollo y determinarán las rutas celulares implicadas y las señales extracelulares. Además, evaluarán la influencia de la biomecánica, como la adhesión y la rigidez de los tejidos en la estratificación neuronal. Los resultados nos permitirán comprender mejor el desarrollo retinal en los vertebrados, incluido el ser humano, y cómo surgen las enfermedades en esa membrana.
Objetivo
Neuronal lamination is a hallmark of many diverse brain areas where it is important for efficient circuit formation and neuronal wiring. Despite this significance, the cellular and tissue scale principles that ensure successful and robust lamination are not fully understood. In particular, how cell-tissue interactions and biomechanics influence neuronal lamination is only scarcely explored. To fill this gap, we will use the vertebrate retina with its five neuronal cell types arranged in a highly ordered pattern to investigate the emergence of neuronal lamination.
We will initially use the zebrafish system and employ long term light sheet imaging to reveal the migration behaviour of the different retinal neurons. Based on this, transcriptomics approaches will enable the dissection of cellular pathways and extracellular cues involved in neuronal migration and overall lamination. To dissect how biomechanics influence lamination, we will use Brillouin microscopy to explore the influence of changing tissue stiffness on lamination and test the role of differential adhesion. These combined results will be the basis to expand studies to the human system and ex vivo human organoids to generate insights into human retinal development.
To date, systematic studies investigating molecular pathways in combination with biophysical parameters to understand brain formation across model systems are rare. Due to our previous expertise, we are in an excellent position to perform such interdisciplinary, integrative and interspecies approach. This will unveil common denominators of retinal neuronal lamination in zebrafish, humans and human organoids and thereby reveal the similarities of retinal development in different species and how developmental programs compare in vivo versus ex vivo.
In addition, while this proposal focuses on neural lamination in the retina, findings will also inspire future cross-disciplinary studies investigating neuronal lamination in other parts of the brain.
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
1067-001 LISBOA
Portugal