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Pitx controls amphioxus asymmetric morphogenesis by promoting left-side development and repressing right-side

Chaofan Xing1, Rongrong Pan1, Guangwei Hu1,2

  • 1State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiangan District, Xiamen, 361102, Fujian, China.

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|August 21, 2021
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Pitx gene function is crucial for left-right asymmetry in amphioxus, controlling organ development by inducing left-sided organs and inhibiting right-sided ones. This study reveals Pitx as a key determinant of asymmetric morphogenesis in this basal chordate.

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Area of Science:

  • Developmental Biology
  • Evolutionary Biology
  • Genetics

Background:

  • Left-right (LR) asymmetry is fundamental in bilateral animals.
  • Vertebrate LR asymmetry involves symmetry breaking, asymmetric gene expression, and morphogenesis.
  • Mechanisms of asymmetric morphogenesis in vertebrates remain poorly understood due to complex organ development.

Purpose of the Study:

  • Investigate the role of Pitx gene function in amphioxus asymmetric organogenesis.
  • Elucidate the molecular mechanisms underlying LR asymmetry in a basal chordate model.
  • Compare LR asymmetry mechanisms between amphioxus and vertebrates.

Main Methods:

  • Studied Pitx gene function in amphioxus.
  • Utilized Pitx null and partial loss-of-function mutations.
  • Analyzed Pitx expression patterns during development.
  • Investigated gene expression changes in response to Pitx manipulation.
  • Identified Pitx binding sites in regulatory sequences of target genes.

Main Results:

  • Pitx null mutation in amphioxus leads to loss of left-sided organs and ectopic right-sided organs on the left.
  • Pitx partial loss-of-function causes milder defects in LR organ formation.
  • Pitx regulates the expression of genes essential for left-sided organ development and represses genes for right-sided organ development.
  • Pitx directly binds to regulatory regions of target genes to control their expression.

Conclusions:

  • Pitx is a major determinant of asymmetric morphogenesis in amphioxus.
  • Different LR organs exhibit distinct requirements for Pitx activity.
  • Pitx controls amphioxus LR morphogenesis by inducing left-sided and inhibiting right-sided organ development.
  • Findings offer insights into vertebrate LR organ development and explain differences in organ positioning between amphioxus and vertebrates.