• organoids
• assembloids
• neurodevelopment
• neocortex
• spinal cord

The development of the nervous system in humans begins with the appearance of the neural plate, which will later give rise to the neural tube. Guided by gradients of morphogens along its axes, the neural tube forms the brain rostrally and the spinal cord caudally. At the level of the telencephalon, neural stem/progenitor cells differentiate into neurons, which will form the layers of the cortex. In the spinal cord, the progenitors generate the different domains of interneurons and motor neurons. During development, the neocortex and the spinal cord interact generating the corticospinal tract, a structure essential for the control of voluntary movements.
New knowledge in cell reprogramming and developmental molecular pathways made it possible to generate 3D human models, called organoids. They can mimic in vitro a wide variety of organs, including the brain and the spinal cord. Recently, organoids with different identities were also fused to generate assembloids.
This thesis aims to generate and characterize cortical and spinal organoids, as well as cortico-spinal assembloids derived from their fusion. Both types of organoids have been successfully generated. Early in development, they show the expression of typical progenitor markers and the formation of ventricle-like architectures. At later stages, cortical organoids show expression of markers typical of the cortical layers, while spinal organoids express markers of both interneurons and motor neurons. In the assembloids, it was possible to appreciate corticofugal projections originating from neurons of the cortical portion.
These models could represent important tools for studying impairments to the corticospinal tract and testing regenerative medicine approaches.