title: Cdx mediates neural tube closure through transcriptional regulation of the planar cell polarity gene Ptk7.
abstract: The vertebrate Cdx genes (Cdx1, Cdx2 and Cdx4) encode homeodomain transcription factors with well-established roles in anteroposterior patterning. To circumvent the peri-implantation lethality inherent to Cdx2 loss of function, we previously used the Cre-loxP system to ablate Cdx2 at post-implantation stages and confirmed a crucial role for Cdx2 function in events related to axial extension. As considerable data suggest that the Cdx family members functionally overlap, we extended this analysis to assess the consequence of concomitant loss of both Cdx1 and Cdx2. Here, we report that Cdx1-Cdx2 double mutants exhibit a severely truncated anteroposterior axis. In addition, these double mutants exhibit fused somites, a widened mediolateral axis and craniorachischisis, a severe form of neural tube defect in which early neurulation fails and the neural tube remains open. These defects are typically associated with deficits in planar cell polarity (PCP) signaling in vertebrates. Consistent with this, we found that expression of Ptk7, which encodes a gene involved in PCP, is markedly reduced in Cdx1-Cdx2 double mutants, and is a candidate Cdx target. Genetic interaction between Cdx mutants and a mutant allele of Scrib, a gene involved in PCP signaling, is suggestive of a role for Cdx signaling in the PCP pathway. These findings illustrate a novel and pivotal role for Cdx function upstream of Ptk7 and neural tube closure in vertebrates.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
authors.forename: Joanne G A
authors.initials: JG
authors.lastname: Savory
authors.forename: Melissa
authors.initials: M
authors.lastname: Mansfield
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Rijli
authors.forename: David
authors.initials: D
authors.lastname: Lohnes
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D000071616:CDX2 Transcription Factor; D016764:Cell Polarity / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D054259:Neural Tube / Q000196:embryology* / Q000378:metabolism*; D054261:Neurulation / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020794:Receptor Protein-Tyrosine Kinases; D014157:Transcription Factors; C487514:Cdx2 protein, mouse; C508433:scrib protein, mouse; C486452:Ptk7 protein, mouse