Disease relevance of Olig2

• We find that infections with Shh-expressing retrovirus at embryonic day 9.5, result in ectopic Olig2 and PDGFR(alpha) expression by mid-embryogenesis [1].
• Expression pattern of the transcription factor Olig2 in response to brain injuries: implications for neuronal repair [2].
• To examine the function of Olig2 in brain lesion, we injected retroviral vectors containing a dominant negative form of Olig2 into the lesioned cortex 2 days after a stab wound [2].

High impact information on Olig2

• Olig2 is required for oligodendrocyte and motor neuron specification in the spinal cord [3].
• Previous studies have shown that Olig2 primes pMN cells to become motor neurons by triggering the expression of Ngn2 and Lhx3 [4].
• Olig2 is a bHLH-class transcription factor in pMN cells, but it has remained unclear how its transcriptional activity is modulated to first produce motor neurons and then oligodendrocytes [4].
• This regionalization of the adult precursor cells is further supported by the restricted expression of the transcription factor Olig2, which specifies transit-amplifying precursor fate and opposes the neurogenic role of Pax6 [5].
• In the absence of Nkx6 genes or Shh signaling, the initial expression of Olig2 in the pMN domain is completely abolished [6].

Biological context of Olig2

• The co-expression of Nkx2.2 and Olig2 in OLPs is tightly associated with myelin gene expression in the normal and PDGFA(-/-) embryos, suggesting a cooperative role of these transcription factors in the control of oligodendrocyte differentiation [7].
• We observed prominent down-regulation of most transcription factors present in telencephalic precursors upon growth factor exposure in neurosphere cultures while Olig1 and Olig2 expression was strongly up-regulated [8].
• Finally, differentiation of mOP cells was accompanied by up-regulation of mRNA encoding Olig2 but not Olig1, which is consistent with previous findings showing that Olig2 is necessary for specification of oligodendrocytes [9].
• An oligodendrocyte-specific zinc-finger transcription regulator cooperates with Olig2 to promote oligodendrocyte differentiation [10].
• When the Olig2-expressing cells at E12.5 were permanently modified to express the lacZ or EGFP gene by tamoxifen-induced Cre-mediated recombination, the cells marked by reporter gene expression were widely distributed in the basal forebrain by E18.5, some of which expressed neuronal markers [11].

Anatomical context of Olig2

• The ventral generation of oligodendrocytes requires Nkx6-regulated expression of the bHLH gene Olig2 in this domain [6].
• In Nkx6.1 mutant spinal cords, expression of Olig2 in the motoneuron progenitor domain is diminished, and the generation and differentiation of oligodendrocytes are significantly delayed and reduced [12].
• We show that in the forebrain, expression of the early oligodendrocyte markers Olig2, plp/dm20 and PDGFR(alpha) corresponds to regions of Shh expression [1].
• Here we show that Olig2 expression at early stages of development (prior to E16.5) identifies a domain in the developing spinal cord, which contains a heterogeneous population of progenitors that includes stem cells and glial progenitors [13].
• In forebrain, Olig3 was expressed in the dorsal thalamus while Olig2 was complementarily expressed in the ventral thalamus with an adjacent boundary at E12 [14].

Physical interactions of Olig2

• In developing neural tube, the basic helix-loop-helix (bHLH) transcription factor Olig2 interacts with the homeodomain transcription factor Nkx2.2 at two distinct stages [15].

Regulatory relationships of Olig2

• Olig1 and Olig2 are related basic helix-loop-helix factors induced by Shh in the ventral neural tube [16].
• At later times, a cooperative interaction is noted because Nkx2.2 promotes maturation of oligodendrocyte progenitor cells specified by expression of Olig2 [15].

Other interactions of Olig2

• Although expression analyses and gain-of-function experiments suggested that these factors were involved in motoneuron and oligodendrocyte development, they do not clearly define the functional differences between Olig1 and Olig2 [16].
• In particular, the transcription factors (TFs) Olig2, Pax6, and Nkx2.2 have been shown to be important in the specification and/or maturation of the OG lineage [17].
• Olig1 or Olig3, other family members, were expressed in the descendent cells that should have expressed Olig2 [16].
• Moreover, coexpression of Olig2 with Nkx2.2 in the chick neural tube generated cells expressing Sox10, a marker of oligodendroglial precursors [18].
• In the embryonic brain, the Olig2 expression domain is broader than that of Olig1 and does not overlap with an oligodendrocyte progenitor marker, CNP [19].

Analytical, diagnostic and therapeutic context of Olig2

• Coculture of NSFCs trans-fected with Ngn2-HB92 or Olig2 and HB9 with purified chicken skeletal muscle demonstrated frequent contacts that resembled neuromuscular junctions [20].
• Here we have used in situ hybridization to investigate the expression patterns of FgfR1-3 and compare them to the putative OL progenitor markers Olig2, Pdgfralpha and Plp/dm20 as a function of development in vivo, in particular at sites of OL specification, migration or differentiation in the mouse forebrain and cerebellum [21].

References