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XB-ART-52793
Development January 1, 2016; 143 (24): 4654-4664.

Foxn4 promotes gene expression required for the formation of multiple motile cilia.

Campbell EP , Quigley IK , Kintner C .


Abstract
Multiciliated cell (MCC) differentiation involves extensive organelle biogenesis required to extend hundreds of motile cilia. Key transcriptional regulators known to drive the gene expression required for this organelle biogenesis are activated by the related coiled-coil proteins Multicilin and Gemc1. Here we identify foxn4 as a new downstream target of Multicilin required for MCC differentiation in Xenopus skin. When Foxn4 activity is inhibited in Xenopus embryos, MCCs show transient ciliogenesis defects similar to those seen in mutants of Foxj1, a known key regulator of genes required for motile ciliation. RNAseq analysis indicates that Foxn4 co-activates some Foxj1 target genes strongly and many Foxj1 targets weakly. ChIPseq suggests that whereas Foxn4 and Foxj1 frequently bind to different targets at distal enhancers, they largely bind together at MCC gene promoters. Consistent with this co-regulation, cilia extension by MCCs is more severely compromised in foxn4 and foxj1 double mutants than in single mutants. In contrast to Foxj1, Foxn4 is not required to extend a single motile cilium by cells involved in left-right patterning. These results indicate that Foxn4 complements Foxj1 transcriptionally during MCC differentiation, thereby shaping the levels of gene expression required for the timely and complete biogenesis of multiple motile cilia.

PubMed ID: 27864379
PMC ID: PMC5201034
Article link: Development
Grant support: [+]
Genes referenced: tuba4a acta4 cby1 ccna1 cdh8 cep152 e2f4 foxj1 foxj1.2 foxn4 homer1 mcidas notch1 rfx2
Antibodies: Tuba4b Ab5
Morpholinos: foxn4 MO1

GEO Series:
   GSE89271: Xenbase,  NCBI


Article Images: [+] show captions
References:
Anders, 2011, Pubmed [+]


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