CASK loss of function differentially regulates neuronal maturation and synaptic function in human induced cortical excitatory neurons.

ABSTRACT: Loss-of-function (LOF) mutations in CASK cause severe developmental phenotypes, including microcephaly with pontine and cerebellar hypoplasia, X-linked intellectual disability, and autism. Unraveling the pathological mechanisms of CASK-related disorders has been challenging owing to limited human cellular models to study the dynamic roles of this molecule during neuronal maturation and synapse development. Here, we investigate cell-autonomous functions of CASK in cortical excitatory induced neurons (iNs) generated from CASK knockout (KO) isogenic human embryonic stem cells (hESCs) using gene expression, morphometrics, and electrophysiology. While immature CASK KO iNs show robust neuronal outgrowth, mature CASK KO iNs display severe defects in synap

SUBMITTER: McSweeney D 

PROVIDER: S-EPMC9574418 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature