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Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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The heterodimer of NF-κB...
Enzyme-linked Receptors01:00

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Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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Protein Networks02:26

Protein Networks

An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
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Related Experiment Video

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Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

Maximum-entropy network analysis reveals a role for tumor necrosis factor in peripheral nerve development and

Prabhjot S Dhadialla1, Ifije E Ohiorhenuan, Andrew Cohen

  • 1Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065, USA.

Proceedings of the National Academy of Sciences of the United States of America
|July 15, 2009
PubMed
Summary

Maximum-entropy network analysis successfully identifies gene regulatory networks from limited microarray data. This method revealed tumor necrosis factor-alpha (TNF-alpha) is crucial for Schwann cell-axon communication during development.

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Area of Science:

  • Developmental Biology
  • Neuroscience
  • Computational Biology

Background:

  • Gene regulatory interactions are vital for development but inferring them from gene expression data (microarrays) typically requires large datasets.
  • Existing computational methods for analyzing gene expression data are often limited by the need for extensive datasets, posing a challenge for researchers.
  • Understanding Schwann cell-axon interactions is critical for peripheral nervous system development and function.

Purpose of the Study:

  • To demonstrate that maximum-entropy network analysis can effectively extract genetic interactions from limited microarray datasets.
  • To investigate the role of tumor necrosis factor-alpha (TNF-alpha) in Schwann cell-axon interactions using a novel computational approach.
  • To elucidate the mechanisms by which TNF-alpha influences cytoplasmic movement and axon guidance in developing peripheral nerves.

Main Methods:

  • Applied maximum-entropy network analysis to limited microarray datasets to infer gene regulatory interactions.
  • Utilized computational predictions to identify key signaling molecules involved in Schwann cell-axon communication.
  • Conducted in vivo and in vitro experiments using TNF-alpha knockout (TNF-/-) mice and recombinant TNF to validate computational findings.

Main Results:

  • Maximum-entropy network analysis successfully identified significant genetic interactions from sparse microarray data.
  • The analysis pinpointed tumor necrosis factor-alpha (TNF-alpha) as a critical regulator of Schwann cell-axon interactions.
  • Experimental validation confirmed that TNF-alpha deficiency impairs Schwann cell envelopment of axons, and exogenous TNF partially rescues this defect.

Conclusions:

  • Maximum-entropy network analysis is a powerful tool for dissecting gene regulatory networks from limited gene expression data.
  • Tumor necrosis factor-alpha (TNF-alpha) plays a direct and essential role in mediating communication between Schwann cells and axons.
  • TNF-alpha orchestrates cytoplasmic movement and axon guidance, highlighting its importance in peripheral nerve development and repair.