Lhx1/5 control dendritogenesis and spine morphogenesis of Purkinje cells via regulation of Espin

Nature Communications
Nga Chu LuiKin Ming Kwan

Abstract

In the cerebellar cortex, Purkinje cells (PCs) receive signals from different inputs through their extensively branched dendrites and serve as an integration centre. Defects in the dendritic development of PCs thus disrupt cerebellar circuitry and cause ataxia. Here we report that specific inactivation of both Lhx1 and Lhx5 in postnatal PCs results in ataxic mutant mice with abnormal dendritic development. The PCs in the mutants have reduced expression of Espin, an F-actin cytoskeleton regulator. We show that Espin expression is transcriptionally activated by Lhx1/5. Downregulation of Espin leads to F-actin mislocalization, thereby impairing dendritogenesis and dendritic spine maturation in the PCs. The mutant PCs therefore fail to form proper synapses and show aberrant electrophysiological properties. By overexpressing Espin, we can successfully rescue the defects in the mutant PCs. Our findings suggest that Lhx1/5, through regulating Espin expression, control dendritogenesis and spine morphogenesis in postnatal PCs.

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Citations

Jan 9, 2019·American Journal of Physiology. Endocrinology and Metabolism·Maigen BetheaChad S Hunter
Jul 2, 2020·Experimental Neurobiology·Tae-Young LeeHaeyoung Suh-Kim
Feb 26, 2019·Frontiers in Endocrinology·Veerle M Darras
Mar 7, 2021·International Journal of Molecular Sciences·Wing Yip TamKwok-Kuen Cheung
Aug 19, 2021·Cellular and Molecular Life Sciences : CMLS·Donatella FariniClaudio Sette
Aug 12, 2019·ACS Biomaterials Science & Engineering·Yan-Lei FanXi-Qiao Feng

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Datasets Mentioned

BETA
CBX207

Methods Mentioned

BETA
PCR
immunoprecipitation
transfection
transmission electron microscopy
reverse transcription PCR
electrophoresis
Assay
electron microscopy

Software Mentioned

Fiji ImageJ
Imaris

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