PMID- 31430272
OWN - NLM
STAT- MEDLINE
DCOM- 20200227
LR  - 20200309
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 17
IP  - 8
DP  - 2019 Aug
TI  - Chemokine signaling links cell-cycle progression and cilia formation for 
      left-right symmetry breaking.
PG  - e3000203
LID - 10.1371/journal.pbio.3000203 [doi]
LID - e3000203
AB  - Zebrafish dorsal forerunner cells (DFCs) undergo vigorous proliferation during 
      epiboly and then exit the 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 forkhead box j1a (Foxj1a), a master regulator of motile cilia, by 
      stimulating Cyclin D1 expression through extracellular regulated MAP kinase (ERK) 
      1/2 signaling. Mechanistically, Cyclin D1-cyclin-dependent kinase (CDK) 4/6 
      drives G1/S transition during DFC proliferation and phosphorylates Foxj1a, 
      thereby disrupting its association with proteasome 26S subunit, non-ATPase 4b 
      (Psmd4b), a 19S regulatory subunit. This prevents the ubiquitin (Ub)-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.
FAU - Liu, Jingwen
AU  - Liu J
AD  - School of Life Sciences, University of Science and Technology of China, Hefei, 
      China.
FAU - Zhu, Chengke
AU  - Zhu C
AD  - Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of 
      Education, Key Laboratory of Aquatics Science of Chongqing, College of Animal 
      Science in Rongchang Campus, Southwest University, Chongqing, China.
FAU - Ning, Guozhu
AU  - Ning G
AD  - State Key Laboratory of Membrane Biology, Institute of Zoology, University of 
      Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
FAU - Yang, Liping
AU  - Yang L
AD  - State Key Laboratory of Membrane Biology, Institute of Zoology, University of 
      Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
FAU - Cao, Yu
AU  - Cao Y
AD  - State Key Laboratory of Membrane Biology, Institute of Zoology, University of 
      Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
FAU - Huang, Sizhou
AU  - Huang S
AUID- ORCID: 0000-0002-1739-8225
AD  - Development and Regeneration Key Laboratory of Sichuan Province, Department of 
      Anatomy and Histology and Embryology, Chengdu Medical College, Chengdu, China.
FAU - Wang, Qiang
AU  - Wang Q
AUID- ORCID: 0000-0002-8735-8771
AD  - State Key Laboratory of Membrane Biology, Institute of Zoology, University of 
      Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
AD  - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190820
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (CXCR4a protein, zebrafish)
RN  - 0 (Chemokines)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxj1a protein, zebrafish)
RN  - 0 (Left-Right Determination Factors)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Zebrafish Proteins)
SB  - IM
MH  - Animals
MH  - Body Patterning/genetics
MH  - Cell Cycle/physiology
MH  - Cell Division
MH  - Cell Proliferation
MH  - Chemokines/metabolism
MH  - Cilia/*metabolism
MH  - Embryo, Nonmammalian/metabolism
MH  - Forkhead Transcription Factors/metabolism
MH  - G1 Phase Cell Cycle Checkpoints/physiology
MH  - Gene Expression Regulation, Developmental/genetics
MH  - Left-Right Determination Factors/*metabolism
MH  - Morphogenesis
MH  - Receptors, CXCR4/*metabolism/physiology
MH  - Signal Transduction
MH  - Zebrafish/embryology/genetics
MH  - Zebrafish Proteins/*metabolism/physiology
PMC - PMC6716676
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/08/21 06:00
MHDA- 2020/02/28 06:00
PMCR- 2019/08/20
CRDT- 2019/08/21 06:00
PHST- 2019/03/06 00:00 [received]
PHST- 2019/08/06 00:00 [accepted]
PHST- 2019/08/30 00:00 [revised]
PHST- 2019/08/21 06:00 [pubmed]
PHST- 2020/02/28 06:00 [medline]
PHST- 2019/08/21 06:00 [entrez]
PHST- 2019/08/20 00:00 [pmc-release]
AID - PBIOLOGY-D-19-00639 [pii]
AID - 10.1371/journal.pbio.3000203 [doi]
PST - epublish
SO  - PLoS Biol. 2019 Aug 20;17(8):e3000203. doi: 10.1371/journal.pbio.3000203. 
      eCollection 2019 Aug.