PG Student The Chinese University of Hong Kong (CUHK), Hong Kong
Abstract: CDKL5 deficiency disorder (CDD) is an X-linked neurodevelopmental disorder causing by loss of function of a serine/threonine kinase, Cyclin-Dependent-Kinase-Like 5 (CDKL5). The CDD patients suffer from severe neurodevelopment defects and the underlying pathological mechanism is not clear. In previous studies we identified nELAVL as novel substrates of CDKL5. Lack of phosphorylation by CDKL5 leads to altered nELAVL phase separation in rodent models. Induced pluripotent stem cells (iPSCs) derived neuron is a promising human-based model to study neurodevelopment disorders. We established CDD patient-derived neuron model and created an isogenic rescue control by Adenine based editing (ABE). We found increased nELAVL granule formation and increased colocalization between nELAVL granules and P-bodies in CDD neurons. Our findings suggested possible altered granule interaction in CDD neurons, which might lead to pathological outcomes. Investigating the mechanism underlying the interaction between nELAVL and P-bodies would be an intriguing focus for future studies.
Funding Source: This work was supported by Lo Kwee-Seong Biomedical Research Fund (J.I), Faculty Innovation Award (FIA2020/A/04) from the Faculty of Medicine, CUHK (J.I.), Hong Kong RGC ECS 24117220 ( J.I.)
