A spatiotemporal barrier formed by Follistatin is required for left-right patterning

Xin Xin Fu, Ding Hao Zhuo, Ying Jie Zhang, Yun Fei Li, Xiang Liu, Yan Yi Xing, Ying Huang, Yi Fan Wang, Tao Cheng, Dan Wang, Si Han Chen, Yi Jian Chen, Guan Nan Jiang, Fu I. Lu, Yu Feng, Xiao Huang, Jun Ma, Wei Liu, Ge Bai, Peng Fei Xu

Research output: Contribution to journalArticlepeer-review

Abstract

How left-right (LR) asymmetry emerges in a patterning field along the anterior-posterior axis remains an unresolved problem in developmental biology. Left-biased Nodal emanating from the LR organizer propagates from posterior to anterior (PA) and establishes the LR pattern of the whole embryo. However, little is known about the regulatory mechanism of the PA spread of Nodal and its asymmetric activation in the forebrain. Here, we identify bilaterally expressed Follistatin (Fst) as a regulator blocking the propagation of the zebrafish Nodal ortholog Southpaw (Spaw) in the right lateral plate mesoderm (LPM), and restricting Spaw transmission in the left LPM to facilitate the establishment of a robust LR asymmetric Nodal patterning. In addition, Fst inhibits the Activin-Nodal signaling pathway in the forebrain thus preventing Nodal activation prior to the arrival, at a later time, of Spaw emanating from the left LPM. This contributes to the orderly propagation of asymmetric Nodal activation along the PA axis. The LR regulation function of Fst is further confirmed in chick and frog embryos. Overall, our results suggest that a robust LR patterning emerges by counteracting a Fst barrier formed along the PA axis.

Original languageEnglish
Article numbere2219649120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number24
DOIs
Publication statusPublished - 2023

All Science Journal Classification (ASJC) codes

  • General

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