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Left-right asymmetry determination in amphioxus

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Many bilateral animals develop morphological left–right asymmetries. In vertebrates, this asymmetry is established under a sequentially activated gene cascade composing of Cerberus, Nodal, Lefty, Pitx and others. To understand how this genetic network has evolved, we examined the functions of some of these genes in the left-right determination of amphioxus, the most basal living chordate, using our recently developed genetic manipulation methods. We show that similar to their cognates in vertebrates, Cerberus, Nodal, Lefty, and Pitx are sequentially activated in amphioxus embryos (first Cerberus, then Lefty, Pitx, and Nodal), and that knocking- out or overexpressing each of these genes disrupted positioning of left-right organs of amphioxus larvae. We also demonstrate that Hh signaling is asymmetrically activated (right & left) in the first somites of early neurula where Cerberus asymmetrical expression then occurs. By knocking-out and overexpressing components of Hh signaling pathway, we further demonstrate that Hh signaling is necessary and sufficient for Cerberus expression and that disruption of Hh signaling caused defects in left-right asymmetry. This is different from the situation in vertebrates in which Hh signaling is required for maintaining asymmetric expression of Nodal, but not required for Cerberus expression. Together, our results indicate that the core regulatory cassette controlling left–right asymmetry was in place in the ancestor of amphioxus and vertebrates, although important modifications are also found in amphioxus.

This talk is part of the Evolution and Development Seminar Series series.

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