The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje Cells

Summary: Strictly controlled dendrite patterning underlies precise neural connection. Dendrite self-avoidance is a crucial system preventing self-crossing and clumping of dendrites. Although many cell-surface molecules that regulate self-avoidance have been identified, the signaling pathway that orc...

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Bibliographic Details
Main Authors: Ken-ichiro Kuwako, Hideyuki Okano
Format: Article
Language:English
Published: Elsevier 2018-09-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124718313007
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Summary:Summary: Strictly controlled dendrite patterning underlies precise neural connection. Dendrite self-avoidance is a crucial system preventing self-crossing and clumping of dendrites. Although many cell-surface molecules that regulate self-avoidance have been identified, the signaling pathway that orchestrates it remains poorly understood, particularly in mammals. Here, we demonstrate that the LKB1-SIK kinase pathway plays a pivotal role in the self-avoidance of Purkinje cell (PC) dendrites by ensuring dendritic localization of Robo2, a regulator of self-avoidance. LKB1 is activated in developing PCs, and PC-specific deletion of LKB1 severely disrupts the self-avoidance of PC dendrites without affecting gross morphology. SIK1 and SIK2, downstream kinases of LKB1, mediate LKB1-dependent dendrite self-avoidance. Furthermore, loss of LKB1 leads to significantly decreased Robo2 levels in the dendrite but not in the cell body. Finally, restoration of dendritic Robo2 level via overexpression largely rescues the self-avoidance defect in LKB1-deficient PCs. These findings reveal an LKB1-pathway-mediated developmental program that establishes dendrite self-avoidance. : Kuwako and Okano show that the LKB1-SIK axis is essential for establishing dendrite self-avoidance in Purkinje cells by ensuring an appropriate level of dendritic Robo2. This study reveals a pivotal role for the LKB1 kinase pathway in the developmental program orchestrating the spatial configuration of dendrites in mammalian brain. Keywords: dendrite, self-avoidance, Purkinje cell, cerebellum, LKB1, SIK, Robo2
ISSN:2211-1247