Dataset Information

Exposure to GDNF Enhances the Ability of Enteric Neural Progenitors to Generate an Enteric Nervous System.

ABSTRACT: Cell therapy is a promising approach to generate an enteric nervous system (ENS) and treat enteric neuropathies. However, for translation to the clinic, it is highly likely that enteric neural progenitors will require manipulation prior to transplantation to enhance their ability to migrate and generate an ENS. In this study, we examine the effects of exposure to several factors on the ability of ENS progenitors, grown as enteric neurospheres, to migrate and generate an ENS. Exposure to glial-cell-line-derived neurotrophic factor (GDNF) resulted in a 14-fold increase in neurosphere volume and a 12-fold increase in cell number. Following co-culture with embryonic gut or transplantation into the colon of postnatal mice in vivo, cells derived from GDNF-treated neurospheres showed a 2-fold increase in the distance migrated compared with controls. Our data show that the ability of enteric neurospheres to generate an ENS can be enhanced by exposure to appropriate factors.

SUBMITTER: McKeown SJ

PROVIDER: S-EPMC5312076 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Exposure to GDNF Enhances the Ability of Enteric Neural Progenitors to Generate an Enteric Nervous System.

McKeown Sonja J SJ Mohsenipour Mitra M Bergner Annette J AJ Young Heather M HM Stamp Lincon A LA

Stem cell reports 20170112 2

Cell therapy is a promising approach to generate an enteric nervous system (ENS) and treat enteric neuropathies. However, for translation to the clinic, it is highly likely that enteric neural progenitors will require manipulation prior to transplantation to enhance their ability to migrate and generate an ENS. In this study, we examine the effects of exposure to several factors on the ability of ENS progenitors, grown as enteric neurospheres, to migrate and generate an ENS. Exposure to glial-ce ...[more]

PMID: 28089669

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Project description:The enteric nervous system (ENS) arises from the coordinated migration, expansion and differentiation of vagal and sacral neural crest progenitor cells. During development, vagal neural crest cells enter the foregut and migrate in a rostro-to-caudal direction, colonizing the entire gastrointestinal tract and generating the majority of the ENS. Sacral neural crest contributes to a subset of enteric ganglia in the hindgut, colonizing the colon in a caudal-to-rostral wave. During this process, enteric neural crest-derived progenitors (ENPs) self-renew and begin expressing markers of neural and glial lineages as they populate the intestine. Our earlier work demonstrated that the transcription factor Foxd3 is required early in neural crest-derived progenitors for self-renewal, multipotency and establishment of multiple neural crest-derived cells and structures including the ENS. Here, we describe Foxd3 expression within the fetal and postnatal intestine: Foxd3 was strongly expressed in ENPs as they colonize the gastrointestinal tract and was progressively restricted to enteric glial cells. Using a novel Ednrb-iCre transgene to delete Foxd3 after vagal neural crest cells migrate into the midgut, we demonstrated a late temporal requirement for Foxd3 during ENS development. Lineage labeling of Ednrb-iCre expressing cells in Foxd3 mutant embryos revealed a reduction of ENPs throughout the gut and loss of Ednrb-iCre lineage cells in the distal colon. Although mutant mice were viable, defects in patterning and distribution of ENPs were associated with reduced proliferation and severe reduction of glial cells derived from the Ednrb-iCre lineage. Analyses of ENS-lineage and differentiation in mutant embryos suggested activation of a compensatory population of Foxd3-positive ENPs that did not express the Ednrb-iCre transgene. Our findings highlight the crucial roles played by Foxd3 during ENS development including progenitor proliferation, neural patterning, and glial differentiation and may help delineate distinct molecular programs controlling vagal versus sacral neural crest development.

Dataset Information

Exposure to GDNF Enhances the Ability of Enteric Neural Progenitors to Generate an Enteric Nervous System.

Publications

Exposure to GDNF Enhances the Ability of Enteric Neural Progenitors to Generate an Enteric Nervous System.

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