PMID- 10479457
OWN - NLM
STAT- MEDLINE
DCOM- 19991020
LR  - 20091119
IS  - 0012-1606 (Print)
IS  - 0012-1606 (Linking)
VI  - 213
IP  - 2
DP  - 1999 Sep 15
TI  - HNF-3/forkhead homologue-4 influences lung morphogenesis and respiratory
      epithelial cell differentiation in vivo.
PG  - 405-17
AB  - HNF-3/forkhead homologue 4 (HFH-4), a transcription factor of the winged
      helix/forkhead family, is expressed in various tissues including lung, brain,
      oviduct, testis, and embryonic kidney. In order to test whether the
      temporospatial expression of HFH-4 influences lung morphogenesis, HFH-4 was
      expressed in lungs of transgenic mice under control of the surfactant protein C
      (SP-C) promoter. The morphology of the lungs from SP-C/HFH-4 embryos (day 18
      postconception) was distinctly abnormal, and the severity of the alterations
      correlated with the level of transgene expression as detected by in situ
      hybridization. At high levels of expression, HFH-4 altered epithelial cell
      differentiation and inhibited branching morphogenesis. Atypical cuboidal or
      columnar cells lined the lung periphery of SP-C/HFH-4 transgenic mice. The
      atypical epithelial cells seen in the SP-C/HFH-4 mice expressed thyroid
      transcription factor-1 and hepatocyte nuclear factor 3beta (HNF-3beta). However, 
      surfactant proteins SP-B, SP-C, and Clara cell secretory protein, normally
      produced by nonciliated epithelial cells in lung parenchyma were lacking.
      beta-Tubulin IV, a marker of ciliated cells, stained the atypical columnar cells 
      produced by expression of high levels of the SP-C/HFH-4 transgene. Ectopic
      expression of HFH-4 in developing mouse lung altered epithelial cell
      differentiation and morphology, restricting the expression of markers typical of 
      nonciliated cells of the distal lung parenchyma.
CI  - Copyright 1999 Academic Press.
FAU - Tichelaar, J W
AU  - Tichelaar JW
AD  - Division of Pulmonary Biology, Children's Hospital Medical Center, 3333 Burnet
      Avenue, Cincinnati, Ohio, 45229-3039, USA.
FAU - Lim, L
AU  - Lim L
FAU - Costa, R H
AU  - Costa RH
FAU - Whitsett, J A
AU  - Whitsett JA
LA  - eng
GR  - HL 41496/HL/NHLBI NIH HHS/United States
GR  - HL 56387/HL/NHLBI NIH HHS/United States
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  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hepatocyte Nuclear Factor 4)
RN  - 0 (Phosphoproteins)
RN  - 0 (Tcfl4 protein, mouse)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
MH  - Cell Differentiation/physiology
MH  - Cells, Cultured
MH  - *DNA-Binding Proteins
MH  - Epithelial Cells/cytology/physiology
MH  - Gene Expression Regulation, Developmental/physiology
MH  - Hepatocyte Nuclear Factor 4
MH  - Lung/cytology/*embryology
MH  - Mice
MH  - Mice, Transgenic
MH  - Morphogenesis/physiology
MH  - Phosphoproteins/*physiology
MH  - Respiratory System/cytology
MH  - Transcription Factors/*physiology
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.1006/dbio.1999.9380 [doi]
AID - S0012-1606(99)99380-6 [pii]
PST - ppublish
SO  - Dev Biol. 1999 Sep 15;213(2):405-17. doi: 10.1006/dbio.1999.9380.