Understanding the role of paraxis in Nematostella vectensis segmentation

Abstract

Segmentation is a feature of all bilaterian chordates. It is initiated in the early embryo through a process called somitogenesis. The paraxial mesoderm, composed of mesenchymal cells, gives rise to repeated epithelial structures called somites through a mesenchymal-to-epithelial transition. In contrast, the endoderm of the cnidarian sea anemone, Nematostella vectensis, is divided into eight bi-radially positioned segments. Cnidarians are the sister group to bilaterians and like all its members, N. vectensis is diploblastic, containing only two germ layers, and lacking a well-defined mesoderm. Yet, surprisingly, the Nematostella endoderm expresses several genes whose bilaterian orthologs are typically involved in mesoderm patterning and vertebrate somitogenesis. Moreover, several morphological parallels exist between Nematostella segments and vertebrate somites. Taken together, this hints at the possibility of a common origin between the two, suggesting that the molecular mechanisms involved in segmentation were likely present in the last common ancestor of bilateria and cnidaria more than 600 million years ago. This thesis aims to understand the role of paraxis in N. vectensis segmentation, which is orthologous to a vertebrate somitogenesis factor of the same name. In vertebrates, Paraxis is a bHLH transcriptional activator that regulates the mesenchymal-to-epithelial transition of somites and is crucial for somite epithelialization. Paraxis knockout mice display defects in formation of the axial skeleton and somite derivatives during early development and lethality follows shortly after birth. Using an shRNA-mediated gene knockdown approach, the results presented here indicate that in Nematostella, paraxis regulates the organization of cells within the endomesodermal segments. Paraxis knockdown leads to a partial or complete loss of segment boundaries, suggesting that it might be involved in the segmentation program, however, its role in N. vectensis remains unknown.