Modeling the Interaction of Genetic Background and DYRKlA during Neurogenesis among Collaborative Cross Founder ESC-Derived Cerebral Organoids


Alyssa Edwards

Document Type


Publication Date

Summer 2019

JAX Location

In: Student Reports, Summer 2019, The Jackson Laboratory


Genetic diversity amongst mouse strains complicates the application of standard differentiation protocols in embryonic stem cells in vitro. We took a new neural differentiation protocol nd used it to generate brain organoids on a panel of mouse ES cells representative of the founder genotypes of the Collaborative Cross, to interrogate how genetic background influences the response to inhibition of the neurodevelopmental gene Dyris1a. Dyrk1a loss perturbs many steps in neurodevelopment, and is associate with a severe autism spectrum disordera and microcephaly. Chemical inhibition of Dyrk1a led to a reduction in the percentage of cells expressing neural markers and an overall reduction of the size of organoids, though preliminary results indicate that not all mouse strains respond similarly. Future studies will explore the strain differences in response to Dyrk1 a inhibition in more depth. The experimental approach provides a paradigm for studying how other mutations affect neurodevelopment.

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