LIMK1 and LIMK2 regulate cortical development through affecting neural progenitor cell proliferation and migration

Rui Mao,Zhengping Jia,Yan Wei,Wei Xie,Rui Deng,Lifang Han,Yanghong Meng

doi:10.1186/s13041-019-0487-7

Rui Mao, Zhengping Jia + Show 5 more

Open Access

https://doi.org/10.1186/s13041-019-0487-7

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Abstract

LIMK1 and LIMK2 are key downstream targets to mediate the effects of the Rho family small GTPases and p21-activated kinases (PAK) in the regulation of the actin cytoskeleton. LIMKs are also critical for synaptic transmission, plasticity and memory formation. Changes in LIMK signaling are associated with several neurodevelopmental and neurodegenerative diseases, including autism, intellectual disability and Alzheimer’s disease. However, the role of LIMK signaling in brain development remains unknown. In this study, we used LIMK1 KO and LIMK2 KO mice to investigate the role of LIMK signaling in the cerebral cortical development. We found that these KO mice are reduced in the number of pyramidal neurons in upper cortical layers and this reduction is accompanied by a smaller pool of neural progenitor cells and impaired neuronal migration. These results are similar to those found in PAK1 KO mice and suggest that LIMK-dependent actin regulation may play a key role in mediating the effects of PAK1 and Rho signaling in the regulation of cortical development.

Highlights

Mammalian neocortex is a major brain area that is critical for various brain functions, including cognition and sensory perception [1,2,3]
Mao et al Molecular Brain (2019) 12:67 we investigated the role of LIMK1/2 in mouse neocortical development using LIMK1 KO, LIMK2 KO and LIMK1/2 double KO (DKO) mice
We investigated the role of LIMK1/2 in mouse neocortical development by examining neural progenitor cell proliferation, neuronal migration and neocortical layer organization in developing LIMK1 KO, LIMK2 KO and LIMK1/2 DKO mice

Summary

Introduction

Mammalian neocortex is a major brain area that is critical for various brain functions, including cognition and sensory perception [1,2,3]. The precise assembly of neocortex is an essential component of brain development. Abnormities in generation, differentiation or migration of neurons, key processes involved in neocortical development, can cause various neurological and mental disorders, including microcephaly, autism and intellectual disability [4,5,6]. Many molecules and signaling pathways such as Reelin and Notch have been reported to be involved, the exact mechanisms underlying precise cortical development remain unclear [7,8,9,10]. The actin cytoskeleton is a major structural component of the cell and is required for cell morphology and migration, but its role in mouse brain development is poorly understood [11]. We have previously shown that p21-activated kinase 1 (PAK1), a key target of the Rho family small GTPases

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