Requirement for Dlgh-1 in planar cell polarity and skeletogenesis during vertebrate development.
The development of specialized organs is tightly linked to the regulation of cell growth, orientation, migration and adhesion during embryogenesis. In addition, the directed movements of cells and their orientation within the plane of a tissue, termed planar cell polarity (PCP), appear to be crucial for the proper formation of the body plan. In Drosophila embryogenesis, Discs large (dlg) plays a critical role in apical-basal cell polarity, cell adhesion and cell proliferation. Craniofacial defects in mice carrying an insertional mutation in Dlgh-1 suggest that Dlgh-1 is required for vertebrate development. To determine what roles Dlgh-1 plays in vertebrate development, we generated mice carrying a null mutation in Dlgh-1. We found that deletion of Dlgh-1 caused open eyelids, open neural tube, and misorientation of cochlear hair cell stereociliary bundles, indicative of defects in planar cell polarity (PCP). Deletion of Dlgh-1 also caused skeletal defects throughout the embryo. These findings identify novel roles for Dlgh-1 in vertebrates that differ from its well-characterized roles in invertebrates and suggest that the Dlgh-1 null mouse may be a useful animal model to study certain human congenital birth defects.
Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Charlene
C
Rivera
Sara J S
SJ
Simonson
Idella F
IF
Yamben
Shalini
S
Shatadal
Minh M
MM
Nguyen
Maryline
M
Beurg
Paul F
PF
Lambert
Anne E
AE
Griep
D000818:Animals; D001842:Bone and Bones / Q000196:embryology* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics*; D049109:Cell Proliferation; D000074288:Discs Large Homolog 1 Protein; D047108:Embryonic Development / Q000235:genetics*; D005143:Eyelids / Q000254:growth & development / Q000473:pathology; D018095:Germ-Line Mutation; D051528:Guanylate Kinases / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D054259:Neural Tube / Q000254:growth & development / Q000473:pathology; D014714:Vertebrates / Q000235:genetics / Q000254:growth & development
D000074288:Discs Large Homolog 1 Protein; C000614189:Dlg1 protein, mouse; D008565:Membrane Proteins; D051528:Guanylate Kinases