title: FGF signaling is required for brain left-right asymmetry and brain midline formation.
abstract: Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the embryo. Here we uncover a role for FGF signaling that specifically disrupts brain asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM markers southpaw and lefty2 are not affected. However, asymmetrically expressed brain markers lefty1 and cyclops become bilateral. We show that FGF signaling controls expression of six3b and six7, two transcription factors required for repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC (aPKC) and β-catenin protein distribution revealed a midline structure in the forebrain that is dependent on a balance of FGF signaling. Ectopic activation of FGF signaling leads to overexpression of six3b, loss of organized midline adherins junctions and bilateral loss of lefty1 expression. Reducing FGF signaling leads to a reduction in six3b and six7 expression, an increase in cell boundary formation in the brain midline, and bilateral expression of lefty1. Together, these results suggest a novel role for FGF signaling in the brain to control LR asymmetry, six transcription factor expressions, and a midline barrier structure.
authors: Department of Neurobiology & Anatomy, University of Utah School of Medicine, Eccles Institute of Human Genetics, Building 533, Room 3160, 15 North 2030 East, Salt Lake City, UT 84112-5330, United States.
authors: Judith M
authors: JM
authors: Neugebauer
authors: Department of Neurobiology & Anatomy, University of Utah School of Medicine, Eccles Institute of Human Genetics, Building 533, Room 3160, 15 North 2030 East, Salt Lake City, UT 84112-5330, United States. Electronic address: jyost@genetics.utah.edu.
authors: H Joseph
authors: HJ
authors: Yost
mesh_terms: D000818:Animals; D019521:Body Patterning; D001921:Brain / Q000196:embryology* / Q000502:physiology*; D003433:Crosses, Genetic; D005136:Eye Proteins / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D018398:Homeodomain Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D055458:Left-Right Determination Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016548:Prosencephalon / Q000196:embryology; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D000097607:Homeobox Protein SIX3
chemical_list: D005136:Eye Proteins; D005346:Fibroblast Growth Factors; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D009419:Nerve Tissue Proteins; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; D029961:Zebrafish Proteins; D051176:beta Catenin; D000097607:Homeobox Protein SIX3; C572343:Lft2 protein, zebrafish; C114547:Six7 protein, zebrafish; C117508:lft1 protein, zebrafish; C512832:ndr2 protein, zebrafish; C520605:tax1bp3 protein, zebrafish
keywords: Brain asymmetry; FGF signaling; Sine occulis