Nature Communications Paper

29.06.2021

Genikhovich group has a new Nature Communications paper about the regulatory logic of the beta-catenin-dependent axial patterning

In the sea anemone Nematostella, different ectodermally expressed genes react differently to the increasing levels of beta-catenin signaling. Some genes increase their expression to the maximum and expand their initially oral expression domain to cover the whole embryo – we call them “saturating” genes. Others shift their expression domain towards the aboral side upon slight upregulation of beta-catenin signaling and are abolished upon strong upregulation. Curiously, these genes are not simply repressed by beta-catenin signaling because beta-catenin knockdown abolishes them together with the “saturating” genes. Instead, they appear to be following a shifting permissive “window” of beta-catenin signaling intensity. We attempted to find out how “window” behavior worked.

Nematostella embryo at the gastrula stage has two distinct molecular boundaries in the ectoderm – the oral/midbody boundary and the midbody/aboral boundary. By RNA-Seq and gene function analyses, we identified four “saturating” transcription factor genes responsible for the oral identity in Nematostella. They are Brachyury, FoxA, Lmx and FoxB, and without them the “window” genes active in the midbody domain shift their expression orally all the way to the bottom of the forming pharynx. Thus, both “saturating” and “window” genes are positively regulated by beta-catenin. However, specific “saturating” genes are capable of repressing specific “window” genes displacing their expression domain aborally to a specific position.

We noticed also that upregulation of the beta-catenin signaling upon knockdown of the oral “saturating” genes turned the midbody “window” genes into “saturating” genes. Therefore, we thought that the second distinct molecular boundary – the midbody/aboral one – might be regulated by the same principle as the oral/midbody boundary. This proved to be the case, and we identified the responsible transcription factor – Sp6-9.

The regulatory logic we discovered is very similar to how beta-catenin dependent axial patterning works in deuterostomes. We discuss the implications of our findings on our understanding of the evolution of animal body axes.

 

https://www.nature.com/articles/s41467-021-24346-8