11-P016 Cited2 transactivates Nodal expression in the left lateral plate mesoderm through interaction with FoxH1

In contrast to the symmetric appearance from the outside, the vertebrate body shows clear signs of asymmetry on the inside when we consider the distribution of the internal organs. The first sign of asymmetry in the chicken embryo is detected very early in the Hensen’s node, when the left–right asymmetry cascade is being established. One of the earliest molecules asymmetrically expressed is the Ca-dependent cell adhesion molecule N-cadherin. Both mRNA and protein of N-cadherin show a preferential location on the right side of the node. It has been shown that inhibition of N-cadherin function at early stages leads to a left–right mispositioning of the heart, suggesting that N-cadherin plays a role in left–right patterning. In addition of being expressed at the node, later on N-cadherin is expressed in a crescent in the anterior lateral region of the embryo that coincides with the heart prospective region. Data obtained in our laboratory shows that, when we block Ncadherin function at stage 4HH, node cells on the left will mix with the ones on the right possibly being on the basis of the left–right problems described previously. In addition, when Ncadherin is specifically blocked in the heart progenitor region at stage 8HH, the heart shows morphogenetic defects, namely failed looping and multiple chambers. Therefore, our working hypothesis is that different levels of Ncadherin in the node are promoting cell sorting in the node allowing the establishment of laterality and that later on will contribute to the asymmetric morphogenesis of the heart.