| First Author | Kuwako KI | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 11 | Pages | 2808-2818.e4 |
| PubMed ID | 30208308 | Mgi Jnum | J:270632 |
| Mgi Id | MGI:6278579 | Doi | 10.1016/j.celrep.2018.08.029 |
| Citation | Kuwako KI, et al. (2018) The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje Cells. Cell Rep 24(11):2808-2818.e4 |
| abstractText | 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. |
