Common Developmental Requirement for Olig Function Indicates a Motor Neuron/Oligodendrocyte Connection

The oligodendrocyte lineage genes Olig1 and Olig2 encode related bHLH proteins that are coexpressed in neural progenitors. Targeted disruption of these two genes sheds light on the ontogeny of oligodendroglia and genetic requirements for their development from multipotent CNS progenitors. Olig2 is required for oligodendrocyte and motor neuron specification in the spinal cord. Olig1 has roles in development and maturation of oligodendrocytes, evident especially within the brain. Both Olig genes contribute to neural pattern formation. Neither Olig gene is required for astrocytes. These findings, together with fate mapping analysis of Olig-expressing cells, indicate that oligodendrocytes are derived from Olig-specified progenitors that give rise also to neurons.

[1]  Philippe Soriano Generalized lacZ expression with the ROSA26 Cre reporter strain , 1999, Nature Genetics.

[2]  J. Sanes,et al.  Cell lineage in the cerebral cortex of the mouse studied in vivo and in vitro with a Recombinant Retrovirus , 1988, Neuron.

[3]  C. Cepko,et al.  Ectopic expression of Olig1 promotes oligodendrocyte formation and reduces neuronal survival in developing mouse cortex , 2001, Nature Neuroscience.

[4]  W. Richardson,et al.  Dorsal Spinal Cord Neuroepithelium Generates Astrocytes but Not Oligodendrocytes , 1998, Neuron.

[5]  A. McMahon Neural patterning: the role of Nkx genes in the ventral spinal cord. , 2000, Genes & Development.

[6]  W. Richardson,et al.  A singularity of PDGF alpha-receptor expression in the dorsoventral axis of the neural tube may define the origin of the oligodendrocyte lineage. , 1993, Development.

[7]  S. Levison,et al.  Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain , 1993, Neuron.

[8]  W. Richardson,et al.  Oligodendrocyte lineage and the motor neuron connection , 2000, Glia.

[9]  M. Rao,et al.  Gliogenesis in the central nervous system , 2000, Glia.

[10]  D. Rowitch,et al.  Sonic Hedgehog Is Required during an Early Phase of Oligodendrocyte Development in Mammalian Brain , 2001, Molecular and Cellular Neuroscience.

[11]  N. Spassky,et al.  Sonic hedgehog-dependent emergence of oligodendrocytes in the telencephalon: evidence for a source of oligodendrocytes in the olfactory bulb that is independent of PDGFRalpha signaling. , 2001, Development.

[12]  David J Anderson,et al.  Identification of a Novel Family of Oligodendrocyte Lineage-Specific Basic Helix–Loop–Helix Transcription Factors , 2000, Neuron.

[13]  Robert H Miller,et al.  The erbB2 gene is required for the development of terminally differentiated spinal cord oligodendrocytes , 2001, The Journal of cell biology.

[14]  D. Rowitch,et al.  Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Nakafuku,et al.  Combinatorial Roles of Olig2 and Neurogenin2 in the Coordinated Induction of Pan-Neuronal and Subtype-Specific Properties of Motoneurons , 2001, Neuron.

[16]  J. Price Cell lineage in the rat cerebral cortex , 1992, Neurochemistry International.

[17]  Neuronal and glial cell biology , 1991 .

[18]  David J. Anderson,et al.  The bHLH Transcription Factors OLIG2 and OLIG1 Couple Neuronal and Glial Subtype Specification , 2002, Cell.

[19]  D. Rowitch,et al.  Olig bHLH proteins interact with homeodomain proteins to regulate cell fate acquisition in progenitors of the ventral neural tube , 2001, Current Biology.

[20]  T. Jessell,et al.  Coordinate Regulation of Motor Neuron Subtype Identity and Pan-Neuronal Properties by the bHLH Repressor Olig2 , 2001, Neuron.

[21]  François Guillemot,et al.  Crossregulation between Neurogenin2 and Pathways Specifying Neuronal Identity in the Spinal Cord , 2001, Neuron.

[22]  R. Kageyama,et al.  Helix-loop-helix factors in growth and differentiation of the vertebrate nervous system. , 1997, Current opinion in genetics & development.

[23]  G. Fishell,et al.  Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain. , 2001, Development.

[24]  Jacqueline E. Lee Basic helix-loop-helix genes in neural development , 1997, Current Opinion in Neurobiology.

[25]  Silvia Arber,et al.  Requirement for the Homeobox Gene Hb9 in the Consolidation of Motor Neuron Identity , 1999, Neuron.

[26]  R. Skoff Gliogenesis in rat optic nerve: astrocytes are generated in a single wave before oligodendrocytes. , 1990, Developmental biology.

[27]  T. Jessell,et al.  A Homeodomain Protein Code Specifies Progenitor Cell Identity and Neuronal Fate in the Ventral Neural Tube , 2000, Cell.

[28]  R. Hardy Dorsoventral patterning and oligodendroglial specification in the developing central nervous system , 1997, Journal of neuroscience research.

[29]  R. Miller,et al.  Sonic hedgehog signaling is required during the appearance of spinal cord oligodendrocyte precursors. , 1999, Development.

[30]  E. Kandel Nerve cells and behavior. , 1970, Scientific American.

[31]  M. Nakafuku,et al.  Dynamic expression of basic helix-loop-helix Olig family members: implication of Olig2 in neuron and oligodendrocyte differentiation and identification of a new member, Olig3 , 2000, Mechanisms of Development.

[32]  J. Rubenstein,et al.  Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor. , 2001, Development.

[33]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[34]  David J. Anderson,et al.  The bHLH Transcription Factor Olig2 Promotes Oligodendrocyte Differentiation in Collaboration with Nkx2.2 , 2001, Neuron.

[35]  L. Thurlow,et al.  Cell lineage in the rat cerebral cortex: a study using retroviral-mediated gene transfer. , 1988, Development.

[36]  T. Jessell,et al.  Requirement for LIM Homeobox Gene Isl1 in Motor Neuron Generation Reveals a Motor Neuron– Dependent Step in Interneuron Differentiation , 1996, Cell.

[37]  L. Puelles,et al.  Oligodendrocytes originate in a restricted zone of the embryonic ventral neural tube defined by DM-20 mRNA expression , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[38]  Jean-Yves Delattre,et al.  OLIG2 as a specific marker of oligodendroglial tumour cells , 2001, The Lancet.

[39]  D. Rowitch,et al.  Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon. , 2001, Development.

[40]  Joanne Chan,et al.  Sonic Hedgehog–Regulated Oligodendrocyte Lineage Genes Encoding bHLH Proteins in the Mammalian Central Nervous System , 2000, Neuron.

[41]  W. Richardson,et al.  Pax6 Influences the Time and Site of Origin of Glial Precursors in the Ventral Neural Tube , 1998, Molecular and Cellular Neuroscience.

[42]  T. Jessell Neuronal specification in the spinal cord: inductive signals and transcriptional codes , 2000, Nature Reviews Genetics.