Work

Ex Vivo Neurogenesis within Enteric Ganglia Occurs in a PTEN Dependent Manner

Year: 2013

Type: article

Abstract: A population of multipotent stem cells capable of differentiating into neurons and glia has been isolated from adult intestine in humans and rodents. While these cells may provide a pool of stem cells for neurogenesis in the enteric nervous system (ENS), such a function has been difficult to demonstrate in vivo. An extensive study by Joseph et al. involving 108 rats and 51 mice submitted to various insults demonstrated neuronal uptake of thymidine analog BrdU in only 1 rat. Here we introduce a novel approach to study neurogenesis in the ENS using an ex vivo organotypic tissue culturing system. Culturing longitudinal muscle and myenteric plexus tissue, we show that the enteric nervous system has tremendous replicative capacity with the majority of neural crest cells demonstrating EdU uptake by 48 hours. EdU(+) cells express both neuronal and glial markers. Proliferation appears dependent on the PTEN/PI3K/Akt pathway with decreased PTEN mRNA expression and increased PTEN phosphorylation (inactivation) corresponding to increased Akt activity and proliferation. Inhibition of PTEN with bpV(phen) augments proliferation while LY294002, a PI3K inhibitor, blocks it. These data suggest that the ENS is capable of neurogenesis in a PTEN dependent manner.

Source: PLoS ONE

DOI: 10.1371/journal.pone.0059452

Authors: Laren Becker, Johann Peterson, Subhash Kulkarni, Pankaj Jay Pasricha

Institutions: Stanford Medicine, Stanford University, University of California Davis Medical Center, University of California, Davis, Johns Hopkins University

Language: English

Topic: Neurogenesis and neuroplasticity mechanisms

Subfield: Developmental Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,382