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Neural Development in Homo sapiens

Gary Mantalas
Gary Mantalas
Speaker Name: 
Gary Mantalas
Speaker Title: 
Graduate Student, MCD Biology
Speaker Organization: 
Haussler Lab
Start Time: 
Friday, May 17, 2019 - 12:00pm
End Time: 
Friday, May 17, 2019 - 1:00pm
Location: 
Nat Sci Annex 101
Organizer: 
David Haussler

 

Abstract:

Cerebral cortex organoids (cerebral organoids) derived from human pluripotent stem cell lines provide a model system for studying how genetics can affect human brain development. 

 

We recently demonstrated that deletion of human-specific NOTCH2NL genes in human embryonic stem cell (hESC)-derived cortical organoids accelerates differentiation of neural stem cells resulting in smaller organoids with a higher proportion of cells expressing markers of excitatory projection neurons at early time points. This led to the hypothesis that NOTCH2NL expression in the human cortex increases the self-renewal capacity of neural stem cells. 

 

We also found that NOTCH2NLA and NOTCH2NLB flank a genomic locus (Chromosome 1q21.1) that is highly repetitive and is recurrently deleted or duplicated in patients with a variety of neurodevelopmental disorders including autism, schizophrenia, microcephaly and macrocephaly.

Here, I present our findings further exploring the phenotypes of NOTCH2NL deletions and larger deletion events that mimic those observed in patients with 1q21.1 distal deletions by comparing hESC-derived cerebral organoids with a variety of altered genotypes by single cell RNA-seq to determine how these alterations effect early brain development with respect to the proportions of cell types present and the transcriptional profiles of these resulting cell types. 

 

These studies will reveal the relative contributions of NOTCH2NL genes and the other genes in this genomic locus on cerebral organoid development and could provide a model system for exploring ways to mitigate the developmental effects of pathogenic genomic rearrangements at this locus.