PMID- 10873152
OWN - NLM
STAT- MEDLINE
DCOM- 20000814
LR  - 20061115
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 23
IP  - 1
DP  - 2000 Jul
TI  - Ciliogenesis and left-right axis defects in forkhead factor HFH-4-null mice.
PG  - 45-51
AB  - Cilia have been classified as sensory or motile types on the basis of functional 
      and structural characteristics; however, factors important for regulation of 
      assembly of different cilia types are not well understood. Hepatocyte nuclear 
      factor-3/forkhead homologue 4 (HFH-4) is a winged helix/forkhead transcription 
      factor expressed in ciliated cells of the respiratory tract, oviduct, and 
      ependyma in late development through adulthood. Targeted deletion of the Hfh4 
      gene resulted in defective ciliogenesis in airway epithelial cells and randomized 
      left-right asymmetry so that half the mice had situs inversus. In HFH-4-null 
      mice, classic motile type cilia with a 9 + 2 microtubule ultrastructure were 
      absent in epithelial cells, including those in the airways. In other organs, 
      sensory cilia with a 9 + 0 microtubule pattern, such as those on olfactory 
      neuroepithelial cells, were present. Ultrastructural analysis of mutant cells 
      with absent 9 + 2 cilia demonstrated that defective ciliogenesis was due to 
      abnormal centriole migration and/or apical membrane docking, suggesting that 
      HFH-4 functions to direct basal body positioning or anchoring. Evaluation of 
      wild-type embryos at gestational days 7.0 to 7.5 revealed Hfh4 expression in 
      embryonic node cells that have monocilium, consistent with a function for this 
      factor at the node in early determination of left- right axis. Analysis of the 
      node of HFH-4 mutant embryos revealed that, in contrast to absent airway cilia, 
      node cilia were present. These observations indicate that there are independent 
      regulatory pathways for node ciliogenesis compared with 9 + 2 type ciliogenesis 
      in airways, and support a central role for HFH-4 in ciliogenesis and left-right 
      axis formation.
FAU - Brody, S L
AU  - Brody SL
AD  - Department of Medicine, Washington University School of Medicine, St. Louis, 
      Missouri, USA. brodys@msnotes.wustl.edu
FAU - Yan, X H
AU  - Yan XH
FAU - Wuerffel, M K
AU  - Wuerffel MK
FAU - Song, S K
AU  - Song SK
FAU - Shapiro, S D
AU  - Shapiro SD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
SB  - IM
MH  - Abnormalities, Multiple/genetics/metabolism/pathology
MH  - Animals
MH  - Brain/abnormalities
MH  - Centrioles/metabolism/pathology/ultrastructure
MH  - Cilia/metabolism/*pathology/ultrastructure
MH  - Embryonic and Fetal Development
MH  - Epithelial Cells/metabolism/pathology/ultrastructure
MH  - Female
MH  - Gene Deletion
MH  - Histocytochemistry
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Microscopy, Electron
MH  - Microtubules/metabolism/pathology/ultrastructure
MH  - Microvilli/metabolism/pathology/ultrastructure
MH  - Phenotype
MH  - Respiratory System/*embryology/metabolism/*pathology/ultrastructure
MH  - Situs Inversus/genetics/metabolism/*pathology
MH  - Trachea/abnormalities/metabolism/pathology/ultrastructure
EDAT- 2000/06/29 11:00
MHDA- 2000/08/19 11:00
CRDT- 2000/06/29 11:00
PHST- 2000/06/29 11:00 [pubmed]
PHST- 2000/08/19 11:00 [medline]
PHST- 2000/06/29 11:00 [entrez]
AID - 10.1165/ajrcmb.23.1.4070 [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2000 Jul;23(1):45-51. doi: 10.1165/ajrcmb.23.1.4070.