Wnt/Axin1/beta-catenin signaling regulates asymmetric nodal activation, elaboration, and concordance of CNS asymmetries.
Nodal activity in the left lateral plate mesoderm (LPM) is required to activate left-sided Nodal signaling in the epithalamic region of the zebrafish forebrain. Epithalamic Nodal signaling subsequently determines the laterality of neuroanatomical asymmetries. We show that overactivation of Wnt/Axin1/beta-catenin signaling during late gastrulation leads to bilateral epithalamic expression of Nodal pathway genes independently of LPM Nodal signaling. This is consistent with a model whereby epithalamic Nodal signaling is normally bilaterally repressed, with Nodal signaling from the LPM unilaterally alleviating repression. We suggest that Wnt signaling regulates the establishment of the bilateral repression. We identify a second role for the Wnt pathway in the left/right regulation of LPM Nodal pathway gene expression, and finally, we show that at later stages Axin1 is required for the elaboration of concordant neuroanatomical asymmetries.
Carl
Matthias
M
Department of Anatomy and Developmental Biology, UCL, Gower Street, London WC1E 6BT, UK. m.carl@ucl.ac.uk
Bianco
Isaac H
IH
Bajoghli
Baubak
B
Aghaallaei
Narges
N
Czerny
Thomas
T
Wilson
Stephen W
SW
D000818:Animals; D060466:Axin Protein; D004292:Dominance, Cerebral / Q000502:physiology*; D019261:Epithalamus / Q000196:embryology / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D005775:Gastrula / Q000502:physiology; D015870:Gene Expression; D019262:Habenula / Q000166:cytology / Q000196:embryology; D008648:Mesoderm / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000166:cytology; D055457:Nodal Protein; D016548:Prosencephalon / Q000196:embryology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D051176:beta Catenin / Q000502:physiology*
D060466:Axin Protein; D055457:Nodal Protein; D020033:Protein Isoforms; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D051176:beta Catenin