title: BMP regulates regional gene expression in the dorsal otocyst through canonical and non-canonical intracellular pathways.
abstract: The inner ear consists of two otocyst-derived, structurally and functionally distinct components: the dorsal vestibular and ventral auditory compartments. BMP signaling is required to form the vestibular compartment, but how it complements other required signaling molecules and acts intracellularly is unknown. Using spatially and temporally controlled delivery of signaling pathway regulators to developing chick otocysts, we show that BMP signaling regulates the expression of Dlx5 and Hmx3, both of which encode transcription factors essential for vestibular formation. However, although BMP regulates Dlx5 through the canonical SMAD pathway, surprisingly, it regulates Hmx3 through a non-canonical pathway involving both an increase in cAMP-dependent protein kinase A activity and the GLI3R to GLI3A ratio. Thus, both canonical and non-canonical BMP signaling establish the precise spatiotemporal expression of Dlx5 and Hmx3 during dorsal vestibular development. The identification of the non-canonical pathway suggests an intersection point between BMP and SHH signaling, which is required for ventral auditory development.
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132-3401, USA.
authors.forename: Sho
authors.identifier: 0000-0002-2421-8093
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Department of Cell and Developmental Biology and Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Baolin
authors.identifier: 0000-0001-6776-7925
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132-3401, USA Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112-5330, USA.
authors.forename: Suzanne L
authors.identifier: 0000-0001-9040-302X
authors.initials: SL
authors.lastname: Mansour
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132-3401, USA schoenwolf@neuro.utah.edu.
authors.forename: Gary C
authors.identifier: 0000-0003-1764-2619
authors.initials: GC
authors.lastname: Schoenwolf
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002645:Chickens; D003051:Cochlea / Q000196:embryology / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D007758:Ear, Inner / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051857:Otx Transcription Factors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012665:Semicircular Canals / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D000074290:Zinc Finger Protein Gli3
chemical_list: D019485:Bone Morphogenetic Proteins; C501120:Dlx5 protein, mouse; C465571:Gli3 protein, mouse; C086187:Hmx3 protein, mouse; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D051785:Smad Proteins; D000074290:Zinc Finger Protein Gli3; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Chicken; Dorsalization; Inner ear; Otocyst; Polarization; Signaling