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Dendrite development regulated by CREST, a calcium-regulated transcriptional activator

Hiroyuki Aizawa1, Shu-Ching Hu, Kathryn Bobb

  • 1Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Science (New York, N.Y.)
|January 13, 2004
PubMed

Insights

Calcium-responsive transactivator, CREST, is crucial for brain development. It regulates gene expression and neuronal growth, with crest gene disruption causing defects in dendrite development.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Neuronal activity profoundly influences brain development through calcium-dependent gene expression.
  • Understanding the molecular mechanisms linking neuronal activity to developmental changes is essential.

Purpose of the Study:

  • To identify and characterize novel factors mediating calcium-dependent gene expression in the developing brain.
  • To investigate the role of the calcium-responsive transactivator CREST in neuronal development.

Main Methods:

  • Employed the transactivator trap strategy to clone calcium-responsive transactivators.
  • Generated and analyzed mice with a targeted disruption of the crest gene.
  • Examined dendritic development in cortical neurons from wild-type and mutant mice.

Main Results:

  • Successfully cloned a novel calcium-responsive transactivator, CREST, a SYT-related nuclear protein.
  • CREST interacts with cAMP response element-binding protein (CREB)-binding protein (CBP) and is expressed in the developing brain.
  • Mice lacking functional crest gene exhibit impaired cortical and hippocampal dendrite development, with compromised calcium-dependent dendritic growth in cortical neurons.

Conclusions:

  • Calcium activation of CREST-mediated transcription is a key regulator of neuronal morphogenesis.
  • CREST plays a vital role in the structural development of neurons during brain development.

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