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Separated at birth? The functional and molecular divergence of OLIG1 and OLIG2

Nature Reviews Neuroscience volume 13, pages 819–831 (2012)Cite this article

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Key Points

  • The basic helix–loop–helix transcription factors oligodendrocyte transcription factor 1 (OLIG1) and OLIG2 are structurally related within their DNA targeting domains and, to a first approximation, are coordinately expressed during development.

  • Notwithstanding similarities in their protein structure and expression pattern, OLIG1 and OLIG2 have non-overlapping functions during development and in the postnatal brain.

  • Olig2-null mice have a striking developmental phenotype involving total loss of motor neurons and near-complete loss of oligodendrocyte progenitors.

  • The developmental phenotype of Olig1-null mice is more nuanced and largely confined to the oligodendrocyte lineage. However, OLIG1 cooperates with OLIG2 in spinal cord patterning.

  • A broadening body of literature links OLIG2 to human gliomas, and pathobiological functions of OLIG1 are suggested in the repair of demyelinating injuries.

  • The divergent biological and pathobiological functions of OLIG1 and OLIG2 reflect the non-overlapping genetic targets, co-regulator proteins and post-translational modification of these proteins.

Abstract

The basic helix–loop–helix transcription factors oligodendrocyte transcription factor 1 (OLIG1) and OLIG2 are structurally similar and, to a first approximation, coordinately expressed in the developing CNS and postnatal brain. Despite these similarities, it was apparent from early on after their discovery that OLIG1 and OLIG2 have non-overlapping developmental functions in patterning, neuron subtype specification and the formation of oligodendrocytes. Here, we summarize more recent insights into the separate roles of these transcription factors in the postnatal brain during repair processes and in neurological disease states, including multiple sclerosis and malignant glioma. We discuss how the unique functions of OLIG1 and OLIG2 may reflect their distinct genetic targets, co-regulator proteins and/or post-translational modifications.

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Figure 1: The developmental roles of OLIG1 and OLIG2.
Figure 2: OLIG1 and OLIG2 localization.
Figure 3: Downstream gene targets of OLIG1 and OLIG2.
Figure 4: Post-translational modification motifs in OLIG1 and OLIG2.

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Acknowledgements

The authors gratefully acknowledge helpful conversations with W. Richardson (University College London, UK), R. Miller (Case Western Reserve University, USA) and Y. Sun (Dana–Farber Cancer Institute, USA). Work from the authors' laboratories that is cited here was supported by grants from the National Institutes of Health (NS047572 and NS057727 to C.D.S. and NS040511 to D.H.R.) and from the Pediatric Low-Grade Astrocytoma Foundation (grant awarded to C.D.S.). D.H.R. is supported by the Howard Hughes Medical Institute.

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  1. Christopher M. Taylor

    Present address: Present address.,

Authors and Affiliations

  1. Departments of Neurobiology, Harvard Medical School and Cancer Biology, Dana–Farber Cancer Institute, 450 Brookline Avenue, Boston, 02215, Massachusetts, USA

    Dimphna H. Meijer, Michael F. Kane, Shwetal Mehta, Christopher M. Taylor & Charles D. Stiles

  2. Informatics Program, Children's Hospital Boston, 300 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Hongye Liu

  3. Departments of Pediatrics and Neurological Surgery, Howard Hughes Medical Institute, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, 94143, California, USA

    Emily Harrington & David H. Rowitch

  4. EMD Serono Research Institute, 45A Middlesex Turnpike, Billerica, 01821, Massachusetts, USA

    Christopher M. Taylor

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DATABASES

NCBI Gene expression omnibus database

Glossary

Cre-lox fate-mapping

This recombination procedure installs a stable marker protein (usually colorimetric, such as LacZ) into a genetically defined cell type and all of its daughter cells.

Tumour-initiating cells

In tumours with a heterogeneous cell population (such as glioblastoma), these undifferentiated stem-like cells are thought to be responsible for propagating the tumours in serial animal transplantation protocols.

Severe combined immunodeficiency

(SCID). SCID mice are used as a host animal for transplantation experiments with human tumours.

Transit-amplifying cells

Also known as type C cells, these are rapidly dividing neural progenitor cells in the subventricular zone of postnatal brain. They are also the immediate progeny of the more slowly replicating multipotent adult neural stem cells.

Single nucleotide polymorphisms

(SNPs). SNPs are DNA sequence variations that differ among individual members of a biological species or between paired chromosomes in a single individual.

Expression profiling

This procedure identifies the gene types that are expressed in a particular cell type by processing mRNA into cDNA and then annealing the cDNA to gene sequences arrayed onto a solid surface.

SUMOylation

This post-translational modification event involves the covalent ligation of small ubiquitin-like modifier (SUMO) proteins to regulate various cellular processes.

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Meijer, D., Kane, M., Mehta, S. et al. Separated at birth? The functional and molecular divergence of OLIG1 and OLIG2. Nat Rev Neurosci 13, 819–831 (2012). https://doi.org/10.1038/nrn3386

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