Wnt 1

Wnt

• 11 Fzd receptors, 19 ligands
• LRP5/6
• "Reverse" activation -> fast signal
• Wnts
  • Wnt10b -> mutationo causes oligodontia
  • Wnt3a - "canonical ligand"
    • Loss - lethal, decrease - loss of limbs,gonads....
    • Wnt structure
      • palmitoylation
      • LRP and fzd "hug" wnt
      • other modulators of receptors - Znrf3, Rnf43 - E3 ligases that target receptors
        • inhibitors - LGR receptor + RSpondin
        • rspo mutation -> tetra amelia (like wnt3)
        • xenopus study - LGR/rspo tuning of limbs Transcription regulation
• TCF/LEF + corepressor -> repression of tg
• With B-CAT - corepressors are replaced > activation
• robinow syndrome
  • ROR2 gene
  • mutation - skeletal dysplasia , BOSSING, hypertelorism, short limbs, genital hypoplasia, vertebrate segmentation
  • WNT5A
    • opposite effec than 3A (on BCAT pathway)?
    • adding Fz4 - inhibitory effect disappears
    • ROR2 - disablec Wnt5a activatory effects completely --> WNT PCP PATHWAY
  • the original Robinow mutation - wnt5a