PMID- 10469590
OWN - NLM
STAT- MEDLINE
DCOM- 19991223
LR  - 20191210
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 9
IP  - 16
DP  - 1999 Aug 26
TI  - Absence of the tight junctional protein AF-6 disrupts epithelial cell-cell
      junctions and cell polarity during mouse development.
PG  - 880-8
AB  - BACKGROUND: The establishment, maintenance and rearrangement of junctions between
      epithelial cells are extremely important in many developmental, physiological and
      pathological processes. AF-6 is a putative Ras effector; it is also a component
      of tight and adherens junctions, and has been shown to bind both Ras and the
      tight-junction protein ZO-1. In the mouse, AF-6 is encoded by the Af6 gene. As
      cell-cell junctions are important in morphogenesis, we generated a null mutation 
      in the murine Af6 locus to test the hypothesis that lack of AF-6 function would
      cause epithelial abnormalities. RESULTS: Although cell-cell junctions are thought
      to be important in early embryogenesis, homozygous mutant embryos were
      morphologically indistinguishable from wild-type embryos through 6.5 days post
      coitum (dpc) and were able to establish all three germ layers. The earliest
      morphological abnormalities were observed in the embryonic ectoderm of mutant
      embryos at 7.5 dpc. The length of the most apical cell-cell junctions was
      reduced, and basolateral surfaces of those cells were separated by multiple gaps.
      Cells of the embryonic ectoderm were less polarized as assessed by histological
      criteria and lateral localization of an apical marker. Mutant embryos died by 10 
      dpc, probably as a result of placental failure. CONCLUSIONS: AF-6 is a critical
      regulator of cell-cell junctions during mouse development. The loss of
      neuroepithelial polarity in mutants is consistent with a loss of efficacy of the 
      cell-cell junctions that have a critical role in establishing apical/basolateral 
      asymmetry.
FAU - Zhadanov, A B
AU  - Zhadanov AB
AD  - McLaughlin Research Institute, 1520 23rd Street South, Great Falls, Montana
      59405-4900, USA.
FAU - Provance, D W Jr
AU  - Provance DW Jr
FAU - Speer, C A
AU  - Speer CA
FAU - Coffin, J D
AU  - Coffin JD
FAU - Goss, D
AU  - Goss D
FAU - Blixt, J A
AU  - Blixt JA
FAU - Reichert, C M
AU  - Reichert CM
FAU - Mercer, J A
AU  - Mercer JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Afdn protein, mouse)
RN  - 0 (Cadherins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Tjp1 protein, mouse)
RN  - 0 (Zonula Occludens-1 Protein)
RN  - EC 3.6.4.1 (Myosins)
RN  - EC 3.6.4.4 (Kinesin)
SB  - IM
MH  - Animals
MH  - Cadherins/analysis
MH  - Cell Polarity/*physiology
MH  - Ectoderm/chemistry
MH  - Embryonic and Fetal Development/genetics/*physiology
MH  - Endoderm/chemistry
MH  - Genotype
MH  - Kinesin/deficiency/*physiology
MH  - Membrane Proteins/analysis
MH  - Mesoderm/metabolism
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Microscopy, Electron
MH  - Myosins/deficiency/*physiology
MH  - Phenotype
MH  - Phosphoproteins/analysis
MH  - Tight Junctions/*enzymology
MH  - Zonula Occludens-1 Protein
EDAT- 1999/09/02 09:00
MHDA- 2001/03/28 10:01
CRDT- 1999/09/02 09:00
PHST- 1999/09/02 09:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/09/02 09:00 [entrez]
AID - S0960-9822(99)80392-3 [pii]
AID - 10.1016/s0960-9822(99)80392-3 [doi]
PST - ppublish
SO  - Curr Biol. 1999 Aug 26;9(16):880-8. doi: 10.1016/s0960-9822(99)80392-3.