Dystroglycan loss disrupts polarity and beta-casein induction inmammary epithelial cells by perturbing laminin anchoring Page: 4 of 40

                                
and epiblasts of embryoid bodies (Li et al., 2002). DG has been implicated also in
epithelial polarity by the study in Drosophila (Deng et al., 2003) and by over-expression
in a tumorigenic human MEC line (Muschler et al., 2002).
Since DG knockout in mice is embryonic lethal (Williamson et al., 1997), DG functions
have not been assessed by genetic means in adult mammalian epithelial cells. Here we
have used a genetic approach in cultured cells to investigate DG's contribution to
laminin-111-induced epithelial architecture and function. We examined the effect of a
DG gene deletion on laminin assembly and laminin-111-induced responses in adult
mouse MEC lines. Results presented here demonstrate for the first time that DG serves
as a critical MEC co-receptor mediating cell responses to the basement membrane that
include epithelial polarization and (-casein induction. We also dissect the critical
receptor domains and demonstrate that DG enacts these signals by anchoring laminin-111
to the cell surface, thereby facilitating laminin-111 polymerization and subsequent
signaling.

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