title: Wnt3 and Wnt3a are required for induction of the mid-diencephalic organizer in the caudal forebrain.
abstract: BACKGROUND
  A fundamental requirement for development of diverse brain regions is the function of local organizers at morphological boundaries. These organizers are restricted groups of cells that secrete signaling molecules, which in turn regulate the fate of the adjacent neural tissue. The thalamus is located in the caudal diencephalon and is the central relay station between the sense organs and higher brain areas. The mid-diencephalic organizer (MDO) orchestrates the development of the thalamus by releasing secreted signaling molecules such as Shh.
  
  
  RESULTS
  Here we show that canonical Wnt signaling in the caudal forebrain is required for the formation of the Shh-secreting MD organizer in zebrafish. Wnt signaling induces the MDO in a narrow time window of 4 hours - between 10 and 14 hours post fertilization. Loss of Wnt3 and Wnt3a prevents induction of the MDO, a phenotype also observed upon blockage of canonical Wnt signaling per se. Pharmaceutical activation of the canonical Wnt pathways in Wnt3/Wnt3a compound morphant embryos is able to restore the lack of the MDO. After blockage of Wnt signaling or knock-down of Wnt3/Wnt3a we find an increase of apoptotic cells specifically within the organizer primordium. Consistently, blockage of apoptosis restores the thalamus organizer MDO in Wnt deficient embryos.
  
  
  CONCLUSIONS
  We have identified canonical Wnt signaling as a novel pathway, that is required for proper formation of the MDO and consequently for the development of the major relay station of the brain - the thalamus. We propose that Wnt ligands are necessary to maintain the primordial tissue of the organizer during somitogenesis by suppressing Tp53-mediated apoptosis.
authors.affiliation: Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Karlsruhe, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mattes
authors.forename: Sabrina
authors.initials: S
authors.lastname: Weber
authors.forename: João
authors.initials: J
authors.lastname: Peres
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: Gary
authors.initials: G
authors.lastname: Davidson
authors.forename: Corinne
authors.initials: C
authors.lastname: Houart
authors.forename: Steffen
authors.initials: S
authors.lastname: Scholpp
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D016548:Prosencephalon / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D060508:Wnt3 Protein / Q000235:genetics / Q000378:metabolism*; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555512:Wnt3a protein, zebrafish; D029961:Zebrafish Proteins