The zebrafish foxj1a transcription factor regulates cilia function in response to injury and epithelial stretch

被引:63
作者
Hellman, Nathan E. [1 ]
Liu, Yan [1 ]
Merkel, Erin [2 ]
Austin, Christina [2 ]
Le Corre, Stephanie [1 ]
Beier, David R. [3 ]
Sun, Zhaoxia [4 ]
Sharma, Neeraj [5 ]
Yoder, Bradley K. [5 ]
Drummond, Iain A. [1 ,2 ]
机构
[1] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02129 USA
[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA
[4] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06515 USA
[5] Univ Alabama Birmingham, Sch Med, Dept Cell Biol, Birmingham, AL 35294 USA
基金
美国国家卫生研究院;
关键词
pronephros; cystic kidney disease; neural injury; beat rate; ciliogenesis; POLYCYSTIC KIDNEY-DISEASE; URINARY-TRACT OBSTRUCTION; MORPHOLOGICAL-CHANGES; PROTEOMIC ANALYSIS; EXOCRINE PANCREAS; TUBULAR CELLS; MOTILE CILIA; MOUSE MODEL; EXPRESSION; MICE;
D O I
10.1073/pnas.1005998107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cilia are essential for normal organ function and developmental patterning, but their role in injury and regeneration responses is unknown. To probe therole of cilia in injury, we analyzed the function of foxj1, a transcriptional regulator of cilia genes, in response to tissue damage and renal cyst formation. Zebrafish foxj1a, but not foxj1b, was rapidly induced in response to epithelial distension and stretch, kidney cyst formation, acute kidney injury by gentamicin, and crush injury in spinal cord cells. Obstruction-inducedup-regulation of foxj1a was not inhibited by cycloheximide, identifying foxj1a as a primary response gene to epithelial injury. Foxj1 was also dramatically up-regulated in murine cystic kidney disease epithelia [jck/jck ( nek8) and Ift88Tg737Rpw(-/-)] as well as in response to kidney ischemia-reperfusion injury. Obstruction of the zebrafish pronephric tubule caused a rapid increase in cilia beat rate that correlated tightly with expanded tubule diameter and epithelial stretch. Zebrafish foxj1a was specifically required for cilia motility. Enhanced foxj1a expression in obstructed tubules induced ciliamotility target genes efhc1, tektin1, and dnahc9. foxj1a-deficient embryos failed to up-regulate efhc1, tektin-1, and dnahc9 and could not maintain enhanced cilia beat rates after obstruction, identifying an essential role for foxj1 in modulating cilia function after injury. These studies reveal that activation of a Foxj1 transcriptional network of ciliogenic genes is an evolutionarily conserved response to multiple forms of tissue damage and highlight enhanced cilia function as a previously uncharacterized component of organ homeostasis.
引用
收藏
页码:18499 / 18504
页数:6
相关论文
共 59 条
[1]   Isolation and expression analysis of foxi1 and foxi1.2 in zebrafish embryos [J].
Aamar, Emil ;
Dawid, Igor B. .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 2008, 52 (07) :985-991
[2]   TRPV4 channel is involved in the coupling of fluid viscosity changes to epithelial ciliary activity [J].
Andrade, YN ;
Fernandes, J ;
Vázquez, E ;
Fernández-Fernández, JM ;
Arniges, M ;
Sánchez, TM ;
Villalón, M ;
Valverde, MA .
JOURNAL OF CELL BIOLOGY, 2005, 168 (06) :869-874
[3]  
Ashizawa N, 1999, HISTOL HISTOPATHOL, V14, P539, DOI 10.14670/HH-14.539
[4]   Identification of Signaling Pathways Regulating Primary Cilium Length and Flow-Mediated Adaptation [J].
Besschetnova, Tatiana Y. ;
Kolpakova-Hart, Elona ;
Guan, Yinghua ;
Zhou, Jing ;
Olsen, Bjorn R. ;
Shah, Jagesh V. .
CURRENT BIOLOGY, 2010, 20 (02) :182-187
[5]   Mutation of the mouse hepatocyte nuclear factor forkhead homologue 4 gene results in an absence of cilia and random left-right asymmetry [J].
Chen, JC ;
Knowles, HJ ;
Hebert, JL ;
Hackett, BP .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (06) :1077-1082
[6]   REGULATION OF CILIOGENESIS AND PROLIFERATION OF UTERINE EPITHELIUM BY 20-ALPHA-HYDROXY-PREGN-4-EN-3-ONE ADMINISTRATION AND WITHDRAWAL IN OVARIECTOMIZED RABBITS [J].
CONTI, CJ ;
CONNER, EA ;
GIMENEZCONTI, IB ;
SILVERBERG, SG ;
GERSCHENSON, LE .
BIOLOGY OF REPRODUCTION, 1981, 24 (04) :903-911
[7]   Disruption of intraflagellar in adult mice leads to transport obesity and slow-onset cystic kidney disease [J].
Davenport, James R. ;
Watts, Amanda J. ;
Roper, Venus C. ;
Croyle, Mandy J. ;
van Groen, Thomas ;
Wyss, J. Michael ;
Nagy, Tim R. ;
Kesterson, Robert A. ;
Yoder, Bradley K. .
CURRENT BIOLOGY, 2007, 17 (18) :1586-1594
[8]  
DUFFY JL, 1968, AM J PATHOL, V53, P609
[9]   Cilia localization is essential for in vivo functions of the Joubert syndrome protein Arl13b/Scorpion [J].
Duldulao, Neil A. ;
Lee, Sunjin ;
Sun, Zhaoxia .
DEVELOPMENT, 2009, 136 (23) :4033-4042
[10]   Perinatal differential diagnosis of cystic kidney disease and urinary tract obstruction:: anatomic pathologic, ultrasonographic and genetic findings [J].
Friedmann, W ;
Vogel, M ;
Dimer, JS ;
Luttkus, A ;
Büscher, U ;
Dudenhausen, JW .
EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY, 2000, 89 (02) :127-133