Functional analysis of the mouse Nodal antagonist, Cerl2, during left-right axis formation

Inacio, Jose M; Marques, Sara; Belo, José A.

http://hdl.handle.net/10400.1/11181

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Authors

Inacio, Jose M

Marques, Sara

Belo, José A.

Abstract(s)

Although recently our understanding of how the LR asymmetry is generated in vertebrate embryos has seen rapid progress, many important questions remain to be explained. In mouse embryos, the leftward flow of the extra-embryonic fluid in the node cavity, called nodal flow, seems to be the symmetry-breaking event. However, it is not yet know how this flow functions or how the asymmetric signal(s) generated in the node is/are transferred to the lateral plate mesoderm. The mouse gene cerberus-like2(cerl2) encodes a 20-kDa protein with a predicted signal peptide sequence and a cysteine-rich domain (CRD) containing nine cysteines characteristic of the Cerberus/DAN family. Whole-mount in situ hybridization studies showed that cerl2 transcripts could be first detected in a horseshoe-shaped expression pattern in the perinodal region of the mouse embryo (E7.0), resembling Nodal expression at this stage. At stage E7.5, expression of cerl2 begins to decrease in intensity on the left side, and by early somitogenesis (E8.0), it can be strongly detected in the right side of the node, assuming a complementary expression pattern to that observed in Nodal. Furthermore, it was shown that Cerl2 activity is upstream of the Nodal receptor inhibiting Nodal and its downstream targets. A physical interaction between these two proteins exists, which suggests that Cerl2 is a secreted Nodal antagonist. Here, to elucidate the role of Cerl2 protein in the early events of symmetry breaking the functional activity of this Nodal antagonist will be discussed.