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Netrin-1-mediated axon guidance in mouse embryonic stem cells overexpressing neurogenin-1.

Publication ,  Journal Article
Hill, GW; Purcell, EK; Liu, L; Velkey, JM; Altschuler, RA; Duncan, RK
Published in: Stem Cells Dev
October 10, 2012

Stem cell therapy holds great promise for treating neurodegenerative disease, but major barriers to effective therapeutic strategies remain. A complete understanding of the derived phenotype is required for predicting cell response once introduced into the host tissue. We sought to identify major axonal guidance cues present in neurons derived from the transient overexpression of neurogenin-1 (Neurog1) in mouse embryonic stem cells (ESCs). Neurog1 upregulated the netrin-1 axon guidance receptors DCC (deleted in colorectal cancer) and neogenin (NEO1). Quantitative polymerase chain reaction results showed a 2-fold increase in NEO1 mRNA and a 36-fold increase in DCC mRNA in Neurog1-induced compared with control ESCs. Immunohistochemistry indicated that DCC was primarily expressed on cells positive for the neuronal marker TUJ1. DCC was preferentially localized to the cell soma and growth-cones of induced neurons. In contrast, NEO1 expression showed less specificity, labeling both TUJ1-positive and TUJ1-negative cells as well as uninduced control cells. Axonal outgrowth was directed preferentially toward aggregates of HEK293 cells secreting a recombinant active fragment of netrin-1. These data indicate that DCC and NEO1 are downstream products of Neurog1 and may guide the integration of Neurog1-induced ESCs with target cells secreting netrin-1. Differential expression profiles for netrin receptors could indicate different roles for this guidance cue on neuronal and non-neuronal cells.

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Published In

Stem Cells Dev

DOI

EISSN

1557-8534

Publication Date

October 10, 2012

Volume

21

Issue

15

Start / End Page

2827 / 2837

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tumor Suppressor Proteins
  • Tubulin
  • Time-Lapse Imaging
  • Receptors, Cell Surface
  • Protein Transport
  • Neurons
  • Netrin-1
  • Netrin Receptors
  • Nerve Tissue Proteins
 

Citation

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Hill, G. W., Purcell, E. K., Liu, L., Velkey, J. M., Altschuler, R. A., & Duncan, R. K. (2012). Netrin-1-mediated axon guidance in mouse embryonic stem cells overexpressing neurogenin-1. Stem Cells Dev, 21(15), 2827–2837. https://doi.org/10.1089/scd.2011.0437
Hill, Gerhard W., Erin K. Purcell, Liqian Liu, John Matthew Velkey, Richard A. Altschuler, and Robert Keith Duncan. “Netrin-1-mediated axon guidance in mouse embryonic stem cells overexpressing neurogenin-1.Stem Cells Dev 21, no. 15 (October 10, 2012): 2827–37. https://doi.org/10.1089/scd.2011.0437.
Hill GW, Purcell EK, Liu L, Velkey JM, Altschuler RA, Duncan RK. Netrin-1-mediated axon guidance in mouse embryonic stem cells overexpressing neurogenin-1. Stem Cells Dev. 2012 Oct 10;21(15):2827–37.
Hill, Gerhard W., et al. “Netrin-1-mediated axon guidance in mouse embryonic stem cells overexpressing neurogenin-1.Stem Cells Dev, vol. 21, no. 15, Oct. 2012, pp. 2827–37. Pubmed, doi:10.1089/scd.2011.0437.
Hill GW, Purcell EK, Liu L, Velkey JM, Altschuler RA, Duncan RK. Netrin-1-mediated axon guidance in mouse embryonic stem cells overexpressing neurogenin-1. Stem Cells Dev. 2012 Oct 10;21(15):2827–2837.
Journal cover image

Published In

Stem Cells Dev

DOI

EISSN

1557-8534

Publication Date

October 10, 2012

Volume

21

Issue

15

Start / End Page

2827 / 2837

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tumor Suppressor Proteins
  • Tubulin
  • Time-Lapse Imaging
  • Receptors, Cell Surface
  • Protein Transport
  • Neurons
  • Netrin-1
  • Netrin Receptors
  • Nerve Tissue Proteins