FOXN4

forkhead box N4

Ensembl:
ENSG00000139445
UniProt:
Q96NZ1
OMIM:
609429

Cilia effects upon perturbation of FOXN4

Loss-of-function effect:
Defective ciliogenesis

Ciliogenesis screen results (5 screens)

  • Kim2016: No effect
  • Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-5.54) PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
  • Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381
  • Pusapati et al. 2018 (CRISPR) [CRISPR]: Negative Regulator (Hh signaling, pos_rank=104, lfc=0.76) PMID:30270045

Phenotypes

Mouse phenotype:
increased total body fat amount, no spontaneous movement, decreased prepulse inhibition, preweaning lethality, incomplete penetrance, abnormal spleen morphology, decreased lean body mass, abnormal tooth color, abnormal skin morphology, increased cd4-positive, cd25-positive, alpha-beta regulatory t cell number
Mouse ciliopathy phenotype:
abnormal reti vasculature morphology, abnormal cranium morphology

Subcellular localization

basal body, nucleus

Functional category

  • Ciliary assembly/disassembly
  • Muscle contraction & physiology

Function

Downstream target of Multicilin required for multiciliated cells differentiation (MCC). Complements Foxj1 transcriptio lly by co- activating Foxj1 target genes. Ensures robust gene expression during MCC differentiation, allowing large numbers of specialized organelles to be assembled. When Foxn4 activity is inhibited in Xenopus embryos, MCCs show transient ciliogenesis defects similar to those seen in mutants of Foxj1. Foxn4 promotes gene expression required for the formation of multiple motile cilia (27864379)

Model organism evidence

Mus musculus (2 references)

Foxn3 is part of a transcriptional network that regulates primary cilia in the developing retina.

PMIDs: 41766387, 39554069

C. elegans (1 reference)

In vertebrates, FoxJ1 and FoxN4 Forkhead (FKH) TFs work with RFX in the direct activation of ciliome genes, exclusively in motile cilia cell-types.

PMIDs: 37449480

Xenopus (1 reference)

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.

PMIDs: 27864379