AUTHOR=Kajikawa Eriko , Miki Toru , Takeda Masayoshi , Kiyonari Hiroshi , Hamada Hiroshi 

TITLE=Left-right asymmetric expression of the Nodal-Lefty-Pitx2 module in developing turtle forebrain

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.929808

DOI=10.3389/fcell.2022.929808

ISSN=2296-634X

ABSTRACT=The epithalamus of zebrafish shows morphological and molecular left-right (L-R) asymmetry, but such asymmetry is not apparent in tetrapods. To provide further insight into the evolutionary diversity of brain L-R asymmetry, we have now examined the developing brain of reptile embryos for expression of Nodal, Lefty, and Pitx2. Two turtle species, the Chinese softshell turtle and the red-eared slider turtle, manifested left-sided expression of these three genes in the developing forebrain, with this expression occurring after Nodal expression at the lateral plate and the L-R organizer has disappeared. Nodal activity, as revealed by detection of phosphorylated Smad2/3, was also apparent in the neural epithelium on the left side in both turtle species. In the Chinese softshell turtle, the habenula did not show apparent asymmetry in size and the parapineal organ was absent, but expression of Kctd12 in the habenula occurred predominantly on the left side. In contrast to the turtles, L-R asymmetric expression of Nodal, Lefty, or Pitx2 was not detected in the developing brain of the Madagascar ground gecko. The transcriptional enhancer (ASE) responsible for asymmetric expression of Nodal, Lefty, and Pitx2 was conserved among reptiles including the Chinese softshell turtle and Madagascar ground gecko. Our findings suggest that Nodal, Lefty, and Pitx2 have the potential to be asymmetrically expressed in the developing brain of vertebrates, but that their expression varies even among reptiles.