Shaker, M. R. | bioRxiv Science

bioRxiv2020

Self-Organizing 3D Human Choroid Plexus-Ventricle-Cortical Organoids

Both the choroid plexus (CP) and the cortex are derived from the rostral neural tube during early embryonic development. In addition to producing CSF, the CP secretes essential factors that orchestrate cortical development and later neurogenesis. Previous brain modeling efforts with human pluripotent stem cells (hPSCs) generated either cortical or CP tissues in 3D culture. Here, we used hPSC-derived neuroectodermal cells, the building blocks of the anterior body, to simultaneously generate CP that forms ventricles and cortical cells in organoids (CVCOs), which can be maintained as 3D organoid cultures. Large scale culture revealed reproducibility of the protocol independent of cell lines, clones or batches. CVCOs contain mature and functional CP that projects multiple cilia into the ventricle-like fluid filled cysts and is in direct contact with appropriately patterned cortical cells. CVCOs thus recapitulate key features of developing forebrain structures observed in in vivo and constitute a useful for dissecting the role of CP in human forebrain development in health and disease.

neuroscience↗

bioRxiv2020

Spatiotemporal contribution of neuromesodermal progenitor-derived neural cells in the elongation of developing mouse spinal cord

During vertebrate development, the posterior end of the embryo progressively elongates in a head-to-tail direction to form the body plan. Recent lineage tracing experiments revealed that bi-potent progenitors, called neuromesodermal progenitors (NMPs), produce caudal neural and mesodermal tissues during axial elongation. However, their precise location and contribution to spinal cord development remain elusive. Here we used NMP-specific markers (Sox2 and BraT) and a genetic lineage tracing system to localize NMP progeny in vivo. NMPs were initially located at the tail tip, but were later found in the caudal neural tube, which is a unique feature of mouse development. In the neural tube, they produced neural stem cells (NSCs) and contributed to the spinal cord gradually along the AP axis during axial elongation. Interestingly, NMP-derived NSCs preferentially contributed to the ventral side first and later to the dorsal side at the lumbar spinal cord level, which may be associated with atypical junctional neurulation in mice. Our current observations detail the contribution of NMP progeny to spinal cord elongation and provide insights into how different species uniquely execute caudal morphogenesis.

developmental biology↗