Right, left and cilia: How asymmetry is established

Semin Cell Dev Biol. 2021 Feb:110:11-18. doi: 10.1016/j.semcdb.2020.06.003. Epub 2020 Jun 20.

Abstract

The initial breaking of left-right (L-R) symmetry in the embryo is controlled by a motile-cilia-driven leftward fluid flow in the left-right organiser (LRO), resulting in L-R asymmetric gene expression flanking the LRO. Ultimately this results in left- but not right-sided activation of the Nodal-Pitx2 pathway in more lateral tissues. While aspects of the initial breaking event clearly vary between vertebrates, events in the Lateral Plate Mesoderm (LPM) are conserved through the vertebrate lineage. Evidence from model systems and humans highlights the role of cilia both in the initial symmetry breaking and in the ability of more lateral tissues to exhibit asymmetric gene expression. In this review we concentrate on the process of L-R determination in mouse and humans.

Keywords: Cilia; Genetic Feedback Loops; Left-Right; Node; Timeline.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Cilia / metabolism*
  • Cilia / ultrastructure
  • Embryo, Mammalian
  • Feedback, Physiological
  • Gene Expression Regulation, Developmental*
  • Homeobox Protein PITX2
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Left-Right Determination Factors / genetics
  • Left-Right Determination Factors / metabolism
  • Mechanotransduction, Cellular / genetics*
  • Mesoderm / growth & development
  • Mesoderm / metabolism*
  • Mesoderm / ultrastructure
  • Mice
  • TRPP Cation Channels / genetics
  • TRPP Cation Channels / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Wnt3 Protein / genetics
  • Wnt3 Protein / metabolism

Substances

  • Homeodomain Proteins
  • Left-Right Determination Factors
  • TRPP Cation Channels
  • Transcription Factors
  • Wnt3 Protein
  • Homeobox Protein PITX2
  • Lefty1 protein, mouse
  • Wnt3 protein, mouse