title: Yap and Taz play a crucial role in neural crest-derived craniofacial development.
abstract: The role of the Hippo signaling pathway in cranial neural crest (CNC) development is poorly understood. We used the Wnt1(Cre) and Wnt1(Cre2SOR) drivers to conditionally ablate both Yap and Taz in the CNC of mice. When using either Cre driver, Yap and Taz deficiency in the CNC resulted in enlarged, hemorrhaging branchial arch blood vessels and hydrocephalus. However, Wnt1(Cre2SOR) mutants had an open cranial neural tube phenotype that was not evident in Wnt1(Cre) mutants. In O9-1 CNC cells, the loss of Yap impaired smooth muscle cell differentiation. RNA-sequencing data indicated that Yap and Taz regulate genes encoding Fox transcription factors, specifically Foxc1. Proliferation was reduced in the branchial arch mesenchyme of Yap and Taz CNC conditional knockout (CKO) embryos. Moreover, Yap and Taz CKO embryos had cerebellar aplasia similar to Dandy-Walker spectrum malformations observed in human patients and mouse embryos with mutations in Foxc1. In embryos and O9-1 cells deficient for Yap and Taz, Foxc1 expression was significantly reduced. Analysis of Foxc1 regulatory regions revealed a conserved recognition element for the Yap and Taz DNA binding co-factor Tead. ChIP-PCR experiments supported the conclusion that Foxc1 is directly regulated by the Yap-Tead complex. Our findings uncover important roles for Yap and Taz in CNC diversification and development.
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Cardiovascular Research Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA junw@bcm.edu jfmartin@bcm.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Hsu
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Idaliz M
authors.initials: IM
authors.lastname: Martinez-Traverso
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Maxson
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Cardiovascular Research Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Dickinson
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Cardiovascular Research Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Wythe
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Cardiovascular Research Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Texas Heart Institute, Houston, TX 77030, USA junw@bcm.edu jfmartin@bcm.edu.
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D049109:Cell Proliferation; D020964:Embryo Loss / Q000473:pathology; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D005145:Face / Q000196:embryology*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006470:Hemorrhage / Q000473:pathology; D006849:Hydrocephalus / Q000196:embryology / Q000473:pathology; D008334:Mandible / Q000473:pathology; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D009432:Neural Crest / Q000196:embryology*; D009436:Neural Tube Defects / Q000473:pathology; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D012886:Skull / Q000196:embryology*; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; C517794:Wwtr1 protein, mouse; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse
keywords: Cranial neural crest; Craniofacial development; Yap and Taz