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.
Highlights
In the cerebellar cortex, Purkinje cells (PCs) receive signals from different inputs through their extensively branched dendrites and serve as an integration centre
The results suggest that inactivation of Lhx1/5 in postnatal PCs leads to nonprogressive ataxia and motor deficits
We found that the morphology and the distribution of dendritic spines in the distal dendrites were fairly irregular in the mutant PCs (Fig. 6a)
Summary
Purkinje cells (PCs) receive signals from different inputs through their extensively branched dendrites and serve as an integration centre. A novel actin regulatory protein, Espin, is found to be downregulated in the PCs of DKO mutants and its gene (Espn) is confirmed to be transcriptionally activated by Lhx1/5.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call