Temporal reduction of LATS kinases in the early preimplantation embryo prevents ICM lineage differentiation

Genes Dev. 2013 Jul 1;27(13):1441-6. doi: 10.1101/gad.219618.113.

Abstract

Cellular localization of the Yes-associated protein (YAP) is dependent on large tumor suppressor (LATS) kinase activity and initiates lineage specification in the preimplantation embryo. We temporally reduced LATS activity to disrupt this early event, allowing its reactivation at later stages. This interference resulted in an irreversible lineage misspecification and aberrant polarization of the inner cell mass (ICM). Complementation experiments revealed that neither epiblast nor primitive endoderm can be established from these ICMs. We therefore conclude that precisely timed YAP localization in early morulae is essential to prevent trophectoderm marker expression in, and lineage specification of, the ICM.

Keywords: Hippo pathway; LATS; inner cell mass; lineage specification; trophectoderm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Blastocyst / cytology*
  • Blastocyst Inner Cell Mass / cytology*
  • Cell Cycle Proteins
  • Cell Differentiation*
  • Cell Lineage
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Genetic Complementation Test
  • Hippo Signaling Pathway
  • Mice
  • Phosphoproteins / metabolism
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • Time Factors
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Phosphoproteins
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • Lats1 protein, mouse
  • Protein Serine-Threonine Kinases