Lhx1/5 is critical in controlling dendritogenesis and spine morphogenesis of Purkinje cells via regulation of Espin
Other conference paper


摘要Introduction: Purkinje cells (PCs), the only output neurons in cerebellar cortex, have extensively branched dendrites to receive signals from different cerebellar neurons and serve as an integration centre in cerebellar cortex. Defects in the dendritic development of PCs thus disrupt cerebellar circuitry and cause ataxia. However, the molecular mechanism of dendritic development remains unclear.

Methods and Results: Our group found that the specific inactivation of both Lhx1 and Lhx5 in postnatal PCs resulted in ataxic mutant mice with abnormal PC dendritic development. The PCs of Lhx1/5 mutants had reduced expression of Espin, a novel F-actin cytoskeleton regulator. We later identified that Espin expression was transcriptionally activated by Lhx1/5. Downregulation of Espin in the PCs caused F-actin mislocalization and impaired dendritogenesis and spine morphogenesis. The mutant PCs could not properly innervate with the pre-synaptic inputs, leading to aberrant electrophysiological properties. By overexpressing Espin in the mutant PCs, we were able to rescue the F-actin localization defects and the dendritic defects in the mutant PCs.

Discussion: Our findings give evidences for a novel pathway controlling dendritic development in which Lhx1/5, through regulating Espin expression, govern dendritogenesis and spine morphogenesis in postnatal PCs.
著者N.C. Lui, W.Y. Tam, C. Gao, J. Huang, C.C. Wang, L. Jiang, W.H. Yung, K.M. Kwan
會議名稱ISDN 2018: 22nd Biennial Meeting of the International Society for Developmental Neuroscience

上次更新時間 2018-25-10 於 12:06