Patterning of papillae on the mouse tongue: A system for the quantitative assessment of planar cell polarity signaling.
The dorsal surface of the mouse tongue is covered by ~7000 papillae, asymmetric epithelial protrusions that are precisely oriented to create a stereotyped macroscopic pattern. Within the context of this large-scale pattern, neighboring papillae exhibit a high degree of local order that minimizes the differences in their orientations. We show here that the orientations of lingual papillae are under the control of the core planar cell polarity (PCP) genes Vangl1, Vangl2, and Celsr1. Using K14-Cre and Nkx2.5-Cre to induce conditional knockout of Vangl1 and/or Vangl2 in the tongue epithelium, we observe more severe disruptions to local order among papillae with inactivation of larger numbers of Vangl genes, a greater role for Vangl2 than Vangl1, and a more severe phenotype with the Vangl2 Looptail (Lp) allele than the Vangl2 null allele, consistent with a dominant negative mode of action of the Vangl2Lpallele. Interestingly, Celsr1-/-tongues show disruption of both local and global order, with many papillae in the anterior tongue showing a reversed orientation. To quantify each of these phenotypes, we have developed and applied three procedures for sampling the orientations of papillae and assessing the degree of order on different spatial scales. The experiments reported here establish the dorsal surface of the mouse tongue as a favorable system for studying PCP control of epithelial patterning.
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yanshu
Y
Wang
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
John
J
Williams
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Amir
A
Rattner
Department of Neurology, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA; Department of Pediatrics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.
Shu
S
Wu
Department of Neurology, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA; Department of Pediatrics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.
Alexander G
AG
Bassuk
Institute of Neuroscience, University of Louvain Medical School and WELBIO, B1200 Brussels, Belgium.
Andre M
AM
Goffinet
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jnathans@jhmi.edu.
Jeremy
J
Nathans
D000483:Alleles; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D017353:Gene Deletion; D018628:Gene Dosage; D055786:Gene Knockout Techniques; D056726:Genetic Association Studies; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice / Q000033:anatomy & histology*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014059:Tongue / Q000033:anatomy & histology* / Q000196:embryology
D002352:Carrier Proteins; C117380:Celsr1 protein, mouse; C431577:Ltap protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; C528120:Vangl1 protein, mouse
Epithelial polarity; Papillae; Patterning; Planar cell polarity