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#Cerberus protein

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chick development-l

Cerberus protein on the left side of chick embryos activates:

At stage when left-right asymmetry established, Sonic hedgehog expressed left of Hensen's node induces Cerberus-related Caronte in left paraxial and lateral plate mesoderm. Caronte functions as high-affinity BMP antagonist binding BMP2, BMP4, BMP7 extracellularly, preventing Smad1/5/8 phosphorylation that normally represses Nodal promoter via interplay with FoxH1 and Smad2. BMP inhibition lifts repression permitting Nodal autoactivation left side, followed by Lefty and Pitx2 expression directing asymmetric organ morphogenesis. Right side lacking Caronte maintains BMP blocking Nodal, explaining indirect Nodal activation by Cerberus.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 12: Cerberus activates Nodal via BMP inhibition in left-right patterning.

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Chick development-ll

Cerberus protein expression in chick embryo regulates:

Cerberus and related Dan family protein expressed in chick hypoblast and anterior endoderm is multifunctional antagonist binding Nodal, BMP and Wnt extracellularly. In left-right patterning, at Hensen's node asymmetric Shh and FGF8 induce Nodal left side, Cerberus on right inhibits Nodal preventing activation of Pitx2 left program that controls heart looping and gut laterality. Knockdown causes bilateral Nodal and heterotaxia. While also regulating head formation anteriorly, in gastrula stage chick its key regulatory role is left-right asymmetry via restriction of Nodal pathway rather than dorso-ventral or neural crest formation.

Ref: Levin et al., Cerberus and left-right asymmetry in chick, Cell 1995, Nodal inhibition.

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