title: Loss of LKB1 leads to impaired epithelial integrity and cell extrusion in the early mouse embryo.
abstract: LKB1/PAR-4 is essential for the earliest polarization steps in Caenorhabditis elegans embryos and Drosophila oocytes. Although LKB1 (also known as STK11) is sufficient to initiate polarity in a single mammalian intestinal epithelial cell, its necessity in the formation and maintenance of mammalian epithelia remains unclear. To address this, we completely remove LKB1 from mouse embryos by generating maternal-zygotic Lkb1 mutants and find that it is dispensable for polarity and epithelia formation in the early embryo. Instead, loss of Lkb1 leads to the extrusion of cells from blastocyst epithelia that remain alive and can continue to divide. Chimeric analysis shows that Lkb1 is cell-autonomously required to prevent these extrusions. Furthermore, heterozygous loss of Cdh1 exacerbates the number of extrusions per blastocyst, suggesting that LKB1 has a role in regulating adherens junctions in order to prevent extrusion in epithelia.
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Room 419, Montréal, QC H3A 1A3, Canada.
authors.forename: Dayana
authors.initials: D
authors.lastname: Krawchuk
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Room 419, Montréal, QC H3A 1A3, Canada Department of Human Genetics, McGill University, 1160 Pine Avenue West, Room 419, Montréal, QC H3A 1A3, Canada.
authors.forename: Shihadeh
authors.initials: S
authors.lastname: Anani
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Room 419, Montréal, QC H3A 1A3, Canada.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Honma-Yamanaka
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Room 419, Montréal, QC H3A 1A3, Canada.
authors.forename: Samantha
authors.initials: S
authors.lastname: Polito
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Room 419, Montréal, QC H3A 1A3, Canada.
authors.forename: Marian
authors.initials: M
authors.lastname: Shafik
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Room 419, Montréal, QC H3A 1A3, Canada Department of Human Genetics, McGill University, 1160 Pine Avenue West, Room 419, Montréal, QC H3A 1A3, Canada yojiro.yamanaka@mcgill.ca.
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Yamanaka
mesh_terms: D055372:AMP-Activated Protein Kinases; D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D017173:Caenorhabditis elegans; D064200:Cdh1 Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004848:Epithelium / Q000196:embryology; D005260:Female; D051379:Mice; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D064200:Cdh1 Proteins; C577585:Fzr1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: Cell extrusion; E-cadherin; Epithelial polarity; Preimplantation; STK11; Serine threonine kinase 11