High content screening of cortical neurons identifies novel regulators of axon growth

Murray G. Blackmore, Darcie L. Moore, Robin P. Smith, Jeffrey L. Goldberg, John Bixby, Vance Lemmon

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Neurons in the central nervous system lose their intrinsic capacity for axon regeneration as they mature, and it is widely hypothesized that changes in gene expression are responsible. Testing this hypothesis and identifying the relevant genes has been challenging because hundreds to thousands of genes are developmentally regulated in CNS neurons, but only a small subset are likely relevant to axon growth. Here we used automated high content analysis (HCA) methods to functionally test 743 plasmids encoding developmentally regulated genes in neurite outgrowth assays using postnatal cortical neurons. We identified both growth inhibitors (Ephexin, Aldolase A, Solute Carrier 2A3, and Chimerin), and growth enhancers (Doublecortin, Doublecortin-like, Kruppel-like Factor 6, and CaM-Kinase II gamma), some of which regulate established growth mechanisms like microtubule dynamics and small GTPase signaling. Interestingly, with only one exception the growth-suppressing genes were developmentally upregulated, and the growth-enhancing genes downregulated. These data provide important support for the hypothesis that developmental changes in gene expression control neurite outgrowth, and identify potential new gene targets to promote neurite outgrowth.

Original languageEnglish
Pages (from-to)43-54
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume44
Issue number1
DOIs
StatePublished - May 1 2010

Fingerprint

Axons
Neurons
Growth
Genes
Kruppel-Like Transcription Factors
Gene Expression
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Growth Inhibitors
Fructose-Bisphosphate Aldolase
Monomeric GTP-Binding Proteins
Microtubules
Regeneration
Plasmids
Down-Regulation
Central Nervous System
Neuronal Outgrowth

Keywords

  • Axon regeneration
  • Corticospinal tract
  • Development
  • Doublecortin
  • High content analysis
  • Kruppel-like transcription factor

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

High content screening of cortical neurons identifies novel regulators of axon growth. / Blackmore, Murray G.; Moore, Darcie L.; Smith, Robin P.; Goldberg, Jeffrey L.; Bixby, John; Lemmon, Vance.

In: Molecular and Cellular Neuroscience, Vol. 44, No. 1, 01.05.2010, p. 43-54.

Research output: Contribution to journalArticle

Blackmore, Murray G. ; Moore, Darcie L. ; Smith, Robin P. ; Goldberg, Jeffrey L. ; Bixby, John ; Lemmon, Vance. / High content screening of cortical neurons identifies novel regulators of axon growth. In: Molecular and Cellular Neuroscience. 2010 ; Vol. 44, No. 1. pp. 43-54.
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