1. FGF signaling is required for brain left-right asymmetry and brain midline formation.
- Author
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Neugebauer JM and Yost HJ
- Subjects
- Animals, Crosses, Genetic, Eye Proteins metabolism, Genotype, Homeodomain Proteins metabolism, In Situ Hybridization, Intracellular Signaling Peptides and Proteins metabolism, Left-Right Determination Factors metabolism, Nerve Tissue Proteins metabolism, Prosencephalon embryology, Receptors, Fibroblast Growth Factor metabolism, Transcription Factors, Zebrafish embryology, beta Catenin metabolism, Homeobox Protein SIX3, Body Patterning, Brain embryology, Brain physiology, Fibroblast Growth Factors metabolism, Gene Expression Regulation, Developmental, Signal Transduction, Zebrafish Proteins metabolism
- 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., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2014
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