Ab. Zhadanov et al., Absence of the tight junctional protein AF-6 disrupts epithelial cell-celljunctions and cell polarity during mouse development, CURR BIOL, 9(16), 1999, pp. 880-888
Background: The establishment, maintenance and rearrangement of junctions b
etween epithelial cells are extremely important in many developmental, phys
iological and pathological processes. AF-6 is a putative Ras effector; it i
s also a component of tight and adherens junctions, and has been shown to b
ind both Ras and the tight-junction protein ZO-1. In the mouse, AF-6 is enc
oded 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 hypothes
is 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 indistinguish
able from wild-type embryos through 6.5 days post coitum (dpc) and were abl
e to establish all three germ layers. The earliest morphological abnormalit
ies were observed in the embryonic ectoderm of mutant embryos at 7.5 dpc. T
he length of the most apical cell-cell junctions was reduced, and basolater
al surfaces of those cells were separated by multiple gaps. Cells of the em
bryonic ectoderm were less polarized as assessed by histological criteria a
nd 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 mou
se development. The loss of neuroepithelial polarity in mutants is consiste
nt with a loss of efficacy of the cell-cell junctions that have a critical
role in establishing apical/basolateral asymmetry.