Assembling a Hippo: the evolutionary emergence of an animal developmental signaling pathway

Trends Biochem Sci. 2024 Aug;49(8):681-692. doi: 10.1016/j.tibs.2024.04.005. Epub 2024 May 9.

Abstract

Decades of work in developmental genetics has given us a deep mechanistic understanding of the fundamental signaling pathways underlying animal development. However, little is known about how these pathways emerged and changed over evolutionary time. Here, we review our current understanding of the evolutionary emergence of the Hippo pathway, a conserved signaling pathway that regulates tissue size in animals. This pathway has deep evolutionary roots, emerging piece by piece in the unicellular ancestors of animals, with a complete core pathway predating the origin of animals. Recent functional studies in close unicellular relatives of animals and early-branching animals suggest an ancestral function of the Hippo pathway in cytoskeletal regulation, which was subsequently co-opted to regulate proliferation and animal tissue size.

Keywords: Capsaspora; Hippo pathway; Yorkie; cytoskeletal dynamics; evolutionary cell biology; unicellular holozoans.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Evolution
  • Evolution, Molecular
  • Hippo Signaling Pathway
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Protein Serine-Threonine Kinases* / genetics
  • Protein Serine-Threonine Kinases* / metabolism
  • Signal Transduction*

Substances

  • Protein Serine-Threonine Kinases
  • Intracellular Signaling Peptides and Proteins