scholarly journals Chemokine signaling links cell-cycle progression and cilia formation for left–right symmetry breaking

PLoS Biology ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. e3000203
Author(s):  
Jingwen Liu ◽  
Chengke Zhu ◽  
Guozhu Ning ◽  
Liping Yang ◽  
Yu Cao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Symmetry Breaking ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Chemokine Signaling ◽  
Cilia Formation

scholarly journals Chemokine signaling links cell cycle progression and cilia formation for left-right symmetry breaking

2019 ◽  
Author(s):  
Jingwen Liu ◽  
Chengke Zhu ◽  
Guozhu Ning ◽  
Liping Yang ◽  
Yu Cao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Symmetry Breaking ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Proteasomal Degradation ◽  
Regulatory Subunit ◽  
Cycle Progression ◽  
Cxcr4 Signaling ◽  
Chemokine Signaling ◽  
Cilia Formation

AbstractZebrafish dorsal forerunner cells (DFCs) undergo vigorous proliferation during epiboly and then exit cell cycle to generate Kupffer’s vesicle (KV), a ciliated organ necessary for establishing left-right (L-R) asymmetry. DFC proliferation defects are often accompanied by impaired cilia elongation in KV, but the functional and molecular interaction between cell-cycle progression and cilia formation remains unknown. Here we show that chemokine receptor Cxcr4a is required for L-R laterality by controlling DFC proliferation and KV ciliogenesis. Functional analysis revealed that Cxcr4a accelerates G1/S transition in DFCs and stabilizes Foxj1a, a master regulator of motile cilia, by stimulating Cyclin D1 expression through ERK1/2 signaling. Mechanistically, Cyclin D1-CDK4/6 drives G1/S transition during DFC proliferation and phosphorylates Foxj1a, thereby disrupting its association with Psmd4b, a 19S regulatory subunit. This prevents the ubiquitin-independent proteasomal degradation of Foxj1a. Our study uncovers a role for Cxcr4 signaling in L-R patterning and provides fundamental insights into the molecular linkage between cell-cycle progression and ciliogenesis.Author summaryDuring the organogenesis of zebrafish L-R organizer named KV, DFCs proliferate rapidly during epiboly and then exit the cell cycle to differentiate into ciliated epithelial KV cells. Cell cycle defects in DFCs are often accompanied by an alteration in KV cilia elongation. However, whether the cell cycle and cilia formation are mechanistically linked remains as an open question. In this study, we report that Cxcr4 signaling is required for DFC proliferation and KV ciliogenesis. We reveal that Cxcl12b/Cxcr4a signaling activates ERK1/2, which then promotes Cyclin D1 expression. Cyclin D1-CDK4/6 accelerates the G1/S transition in DFCs, while also facilitates cilia formation via stabilization of Foxj1a. Notably, Foxj1 undergoes proteasomal degradation via Ub-independent pathway during KV organogenesis. Our study further demonstrates that CDK4 phosphorylates and stabilizes Foxj1a by disrupting its association with Psmd4b, a 19S regulatory subunit. In summary, Cxcl12b/Cxcr4a chemokine signaling links cell cycle progression and cilia formation for L-R symmetry breaking via regulating Cyclin D1 expression.

1955-P: GLP-1R Activation Attenuates Prostate Cancer Growth via Inhibiting Cell Cycle Progression

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1955-P
Author(s):  
TORU SHIGEOKA ◽  
TAKASHI NOMIYAMA ◽  
TAKAKO KAWANAMI ◽  
YURIKO HAMAGUCHI ◽  
TOMOKO TANAKA ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cancer Growth ◽  
Cycle Progression
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