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Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system.

ABSTRACT: In the central nervous system (CNS) of adult mammals, neurogenesis occurs in only two restricted areas, the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Isolation of multipotent progenitor cells from other CNS regions suggests that their neurogenic potential is dictated by local environmental cues. Here, we report that astrocytes in areas outside of the SGZ and SVZ of adult mice express high levels of ephrin-A2 and -A3, which present an inhibitory niche, negatively regulating neural progenitor cell growth. Adult mice lacking both ephrin-A2 and -A3 display active ongoing neurogenesis throughout the CNS. These findings suggest that neural cell replacement therapies for neurodegeneration or injury in the adult CNS may be achieved by manipulating ephrin signaling pathways.

SUBMITTER: Jiao JW

PROVIDER: S-EPMC2438395 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system.

Jiao Jian-Wei JW Feldheim David A DA Chen Dong Feng DF

Proceedings of the National Academy of Sciences of the United States of America 20080618 25

In the central nervous system (CNS) of adult mammals, neurogenesis occurs in only two restricted areas, the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Isolation of multipotent progenitor cells from other CNS regions suggests that their neurogenic potential is dictated by local environmental cues. Here, we report that astrocytes in areas outside of the SGZ and SVZ of adult mice express high levels of ephrin-A2 and -A3, which present an inhibitory niche, negativel ...[more]

PMID: 18562299

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Project description:The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties of both classical TFs and architectural components of chromatin. Since the cloning of the Sox/SOX genes, remarkable progress has been made in illuminating their roles as key players in the regulation of multiple developmental and physiological processes. SOX TFs govern diverse cellular processes during development, such as maintaining the pluripotency of stem cells, cell proliferation, cell fate decisions/germ layer formation as well as terminal cell differentiation into tissues and organs. However, their roles are not limited to development since SOX proteins influence survival, regeneration, cell death and control homeostasis in adult tissues. This review summarized current knowledge of the roles of SOX proteins in control of central nervous system development. Some SOX TFs suspend neural progenitors in proliferative, stem-like state and prevent their differentiation. SOX proteins function as pioneer factors that occupy silenced target genes and keep them in a poised state for activation at subsequent stages of differentiation. At appropriate stage of development, SOX members that maintain stemness are down-regulated in cells that are competent to differentiate, while other SOX members take over their functions and govern the process of differentiation. Distinct SOX members determine down-stream processes of neuronal and glial differentiation. Thus, sequentially acting SOX TFs orchestrate neural lineage development defining neuronal and glial phenotypes. In line with their crucial roles in the nervous system development, deregulation of specific SOX proteins activities is associated with neurodevelopmental disorders (NDDs). The overview of the current knowledge about the link between SOX gene variants and NDDs is presented. We outline the roles of SOX TFs in adult neurogenesis and brain homeostasis and discuss whether impaired adult neurogenesis, detected in neurodegenerative diseases, could be associated with deregulation of SOX proteins activities. We present the current data regarding the interaction between SOX proteins and signaling pathways and microRNAs that play roles in nervous system development. Finally, future research directions that will improve the knowledge about distinct and various roles of SOX TFs in health and diseases are presented and discussed.

Dataset Information

Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system.

Publications

Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system.

Similar Datasets

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