YAP regulates neural progenitor cell number via the TEA domain transcription factor

Genes Dev. 2008 Dec 1;22(23):3320-34. doi: 10.1101/gad.1726608. Epub 2008 Nov 17.

Abstract

Tight control of cell proliferation is essential for proper growth during development and for tissue homeostasis in mature animals. The evolutionarily conserved Hippo pathway restrains proliferation through a kinase cascade that culminates in the inhibition of the transcriptional coactivator YAP. Unphosphorylated YAP activates genes involved in cell proliferation and survival by interacting with a DNA-binding factor. Here we show that during vertebrate neural tube development, the TEA domain transcription factor (TEAD) is the cognate DNA-binding partner of YAP. YAP and TEAD gain of function causes marked expansion of the neural progenitor population, partly owing to their ability to promote cell cycle progression by inducing cyclin D1 and to inhibit differentiation by suppressing NeuroM. Their loss of function results in increased apoptosis, whereas repressing their target genes leads to premature neuronal differentiation. Inhibiting the upstream kinases of the Hippo pathway also causes neural progenitor overproliferation. Thus, the Hippo pathway plays critical roles in regulating neural progenitor cell number by affecting proliferation, fate choice, and cell survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Avian Proteins / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Cycle
  • Cell Cycle Proteins
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation*
  • Chick Embryo
  • Cyclin D
  • Cyclins / metabolism
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Humans
  • Muscle Proteins / physiology*
  • Neural Tube / physiology*
  • Neurons / physiology
  • Neuropeptides / metabolism
  • Nuclear Proteins / physiology*
  • Signal Transduction
  • Stem Cells / physiology*
  • Transcription Factors / physiology*
  • Transfection

Substances

  • Avian Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • Cyclin D
  • Cyclins
  • DNA-Binding Proteins
  • Muscle Proteins
  • NeuroM protein, chicken
  • Neuropeptides
  • Nuclear Proteins
  • TEAD1 protein, human
  • TEAD3 protein, human
  • TEAD4 protein, human
  • Transcription Factors
  • YY1AP1 protein, human