Expression Profiling of Aldh1l1-Precursors in the Developing Spinal Cord Reveals Glial Lineage-Specific Genes and Direct Sox9-Nfe2l1 Interactions

Glia, 2013 · DOI: 10.1002/glia.22538 · Published: September 1, 2013

Simple Explanation

This study investigates the development of glial cells in the spinal cord, focusing on astrocytes and oligodendrocytes. These cells are important for brain function, but their early development is not fully understood. The researchers used a specific marker, Aldh1l1-GFP, to identify and isolate early glial cells. They then analyzed the genes expressed in these cells at different developmental stages. The analysis identified several genes and transcription factors, including Nfe2l1, that play a role in glial development. The study also found that Sox9 directly regulates Nfe2l1 expression, contributing to the understanding of how glial cells are formed.

Study Duration

Not specified

Participants

Aldh1l1-GFP BAC transgenic mice

Evidence Level

Not specified

Key Findings

1
Aldh1l1 is a useful marker for identifying gliogenic lineages during embryonic spinal cord development.
2
The study identified three temporal modules of genes correlated with the radial glial-immature-astrocyte transition.
3
Nfe2l1 promotes astrocyte and oligodendrocyte fate in vitro, and some markers of oligodendrocyte fate in vivo, and is regulated by Sox9.

Research Summary

The study aimed to identify novel regulators of glial development using Aldh1l1-GFP as a marker for gliogenic radial glia and later-stage precursors of developing astrocytes. Gene expression profiling of Aldh1l1+ cells between murine embryonic day 13.5–18.5 generated a database of developmental stage-related markers. The research identified Nfe2l1 as a gliogenic transcription factor that promotes astrocyte and oligodendrocyte maturation under direct Sox9 regulatory control.

Practical Implications

Resource for glial development research

The dataset generated serves as a resource for identifying novel regulators of gliogenesis.

Understanding glial roles in development

Temporal patterns of gene activity in glial precursors suggest defined roles in the developing nervous system that change over time.

Potential therapeutic targets

Identifying key transcription factors like Nfe2l1 provides potential targets for manipulating glial fate in disease or injury.

Study Limitations

1
Conditional deletion of Nfe2l1 in the CNS via nestin-cre revealed a post-natal neurodegenerative phenotype and death by weaning.
2
Currently available astrocyte markers may have limitations in identifying intermediate stages of astrocyte fate acquisition.
3
Further detailed loss-of-function studies will be required to further assess whether this gene is required for glial fate determination.

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