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BDNF activates an NFI-dependent neurodevelopmental timing program by sequestering NFATc4.

Baojin Ding1, Paul R Dobner1, Debra Mullikin-Kilpatrick1

  • 1Department of Microbiology and Physiological Systems and Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01605-2324.

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|February 23, 2018
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Summary
This summary is machine-generated.

Brain-Derived Neurotrophic Factor (BDNF) controls neurodevelopment timing by sequestering NFATc4 in the Golgi. This accelerates gene program derepression, revealing a BDNF-NFATc4 autoregulatory loop.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Brain-Derived Neurotrophic Factor (BDNF) is crucial for neuronal survival, growth, and plasticity.
  • Nuclear Factor of Activated T-cells (NFAT) proteins are transcription factors involved in various cellular processes.
  • The precise mechanisms regulating neurodevelopmental timing are complex and incompletely understood.

Purpose of the Study:

  • To elucidate the novel mechanism by which BDNF regulates neurodevelopmental timing.
  • To investigate the role of NFATc4 sequestration in the Golgi apparatus.
  • To identify autoregulatory loops involving BDNF and NFATc4 in cerebellar granule cells.

Main Methods:

  • Utilized techniques to study protein localization and interactions within Golgi.
  • Investigated gene expression patterns related to temporal occupancy.
  • Analyzed the interplay between BDNF and NFATc4 in cerebellar granule cells.

Main Results:

  • Demonstrated that BDNF extranuclear sequestration of NFATc4 occurs in the Golgi.
  • Showed this mechanism accelerates the derepression of an NFI temporal occupancy gene program.
  • Identified an autoregulatory loop where BDNF and NFATc4 drive the program, including Bdnf expression.

Conclusions:

  • BDNF regulates neurodevelopmental timing through a novel Golgi-based mechanism involving NFATc4 sequestration.
  • This process accelerates the temporal gene program in cerebellar granule cells.
  • An autoregulatory loop involving BDNF and NFATc4 is critical for this developmental timing mechanism.