Netrin-1-mediated axon guidance in mouse embryonic stem cells overexpressing neurogenin-1.
Stem Cells Dev
; 21(15): 2827-37, 2012 Oct 10.
Article
en En
| MEDLINE
| ID: mdl-22512716
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Conos de Crecimiento
/
Proteínas Supresoras de Tumor
/
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
/
Células Madre Embrionarias
/
Factores de Crecimiento Nervioso
/
Proteínas del Tejido Nervioso
Tipo de estudio:
Guideline
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Stem Cells Dev
Asunto de la revista:
HEMATOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos