Combinatorial Roles of Olig2 and Neurogenin2 in the Coordinated Induction of Pan-Neuronal and Subtype-Specific Properties of Motoneurons

Abstract

Distinct classes of neurons are generated at defined times and positions during development of the nervous system. It remains elusive how specification of neuronal identity coordinates with acquisition of pan-neuronal properties. Here we show that basic helix-loop-helix (bHLH) transcription factors Olig2 and Neurogenin2 (Ngn2) play vital roles in the coordinated induction of pan-neuronal and subtype-specific properties of motoneurons. Olig2 and Ngn2 are specifically coexpressed in motoneuron progenitors. Misexpression studies in chick demonstrate the specific, combinatorial actions of Olig2 and Ngn2 in motoneuron generation. Our results further revealed crossregulatory interactions between bHLH and homeodomain transcription factors in the specification of motoneurons. We suggest that distinct classes of transcription factors collaborate to generate motoneurons in the ventral neural tube.

Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms

“…Olig2 is a bHLH transcriptional repressor protein that plays essential roles in the lineage specification of progenitor cells into neuronal subtypes (somatic motor neurons and forebrain cholinergic neurons) and oligodendrocytes during central nervous system development [60][61][62][63][64][65][66]. At early embryonic stages, one key role of Olig2 is to maintain progenitor cells in a replication-competent state [67].…”

nkx2.2apromotes specification and differentiation of a myelinating subset of oligodendrocyte lineage cells in zebrafish

“…In both chicks and mice, the p3 and pMN populations of ventral spinal cord precursor cells express Nkx2.2 and Olig2, respectively, through the period of motor neuron development (Mizuguchi et al, 2001;Novitch et al, 2001;Soula et al, 2001;Sun et al, 2001;Zhou et al, 2001;Fu et al, 2002). In chick embryos, Nkx2.2 + cells then begin to disperse throughout the spinal cord in a pattern characteristic of OPCs (Xu et al, 2000).…”

“…In chick embryos, Nkx2.2 + cells then begin to disperse throughout the spinal cord in a pattern characteristic of OPCs (Xu et al, 2000). At about the same time, Nkx2.2 expression expands dorsally into the Olig2 expression domain (Mizuguchi et al, 2001;Novitch et al, 2001;Sun et al, 2001;Zhou et al, 2001;Fu et al, 2002). Double labeling experiments showed that Nkx2.2 + dispersing cells initially are both Olig2 + and Olig2 − but that later, most cells in the spinal cord white matter are Nkx2.2 + Olig2 + (Zhou et al, 2001;Fu et al, 2002).…”

Visualization of bHLH transcription factor interactions in living mammalian cell nuclei and developing chicken neural tube by FRET

“…The most likely explanation of this interesting pattern is that overexpression of proneural genes may induce neural progenitor differentiation and promote their migration from the medial to the lateral half [50]. However, 20% of cells with similar amounts of bHLH protein expression did stay in the medial half (arrow in Figure 5C-D and data not shown); this was probably owing to the different intracellular competence between these cells and the migrating cells.…”