Available online 12 March 2024, 114752

Loss of MARK1 causes a decrease in dendritic spine density in vivo.

Loss of MARK1 leads to an increase in synaptic GKAP and GluA2.

Forebrain-specific conditional knockout of MARK1 impairs spatial learning.

Forebrain-specific conditional knockout of MARK1 decreases anxiety-like behaviors.

Dendritic spines play a pivotal role in synaptic communication and are crucial for learning and memory processes. Abnormalities in spine morphology and plasticity are observed in neurodevelopmental and neuropsychiatric disorders, yet the underlying signaling mechanisms remain poorly understood. The microtubule affinity regulating kinase 1 (MARK1) has been implicated in neurodevelopmental disorders, and the MARK1 gene shows accelerated evolution in the human lineage suggesting a role in cognition. However, the in vivo role of MARK1 in synaptogenesis and cognitive functions remains unknown. Here we show that forebrain-specific conditional knockout (cKO) of Mark1 in mice causes defects in dendritic spine morphogenesis in hippocampal CA1 pyramidal neurons with a significant reduction in spine density. In addition, we found loss of MARK1 causes synaptic accumulation of GKAP and GluA2. Furthermore, we found that MARK1 cKO mice show defects in spatial learning in the Morris water maze and reduced anxiety-like behaviors in the elevated plus maze. Taken together, our data show a novel role for MARK1 in regulating dendritic spine morphogenesis and cognitive functions in vivo.

© 2024 Published by Elsevier Inc.