Hundreds of genes have been associated with autism & neurodev disorders
But how do these genes impact specific stages in human development?
In a new preprint, @XianglingM took a bold approach & developed CRISPR screens in #assembloids to map 425 genes on interneuron dev stages 👇
But how do these genes impact specific stages in human development?
In a new preprint, @XianglingM took a bold approach & developed CRISPR screens in #assembloids to map 425 genes on interneuron dev stages 👇
To achieve this, @XianglingM & our team generated and screened over 1000 forebrain #assembloids built from parts derived from human pluripotent stem cells
This approach revealed that 46 out of a 425 autism spectrum disorder & other neurodevelopmental disease genes (~11%) expressed in the ventral forebrain interfere with either human GABAErgic cortical interneuron generation or interneuron migration
Surprisingly, loss of the ER-shaping Lunapark (LNPK), which causes a severe encephalopathy in children, disrupts cortical interneuron migration in forebrain #assembloids
These experiments also highlights a dynamic role of the ER in interneuron development.
Check out how, in a reporter stem cell line, the ER is elegantly displaced in front of the nucleus before translocation in human cortical interneurons
Check out how, in a reporter stem cell line, the ER is elegantly displaced in front of the nucleus before translocation in human cortical interneurons
Moving forward, systematically mapping disease risk genes onto inaccessible stages of the protracted human neural development will be essential in identifying convergent & divergent pathways and molecularly distinguish forms of behaviorally-defined disorders
Preprint here: biorxiv.org/content/10.110…
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