Research Highlight:

Focus Among Distraction

Original Research Article:
DA Zannino and B Appel (2009). Olig2+ Precursors Produce Abducens Motor Neurons and Oligodendrocytes in the Zebrafish Hindbrain. J Neurosci. 29 (8): 2322-2333.

Centuries of painstaking contributions to the human brain atlas have resulted in a nearly gridlocked roadmap of neural networks. Relatively recent genetic characterizations in model organisms have shed new light on the developing brain. These developmental studies hold the capacity not only to decode the origins of neural complexity, but may in turn reveal the molecular nature of neurodegenerative diseases. In a recent paper highlighted on the cover of the Journal of Neuroscience, Zannino and colleagues identified neural and glial cell origins in the developing brain, ultimately demonstrating the impact of the olig2 transcription factor on formation of oligodendrocyte progenitor cells (OPCs) and a specific type of motor neuron (MN) in the zebrafish hindbrain.

Oligodendrocytes are the myelinating cell type of the central nervous system. Through myelination of neural fibers in the CNS, oligodendrocytes contribute to rapid propagation of action potentials. Immature oligodendrocyte progenitor cells are specified from neuroepithelial precursor populations, which also give rise to neuronal cell types. The mechanism of specification and subsequent differentiation from precursor populations has been most intimately studied in the spinal cord, where the neural milieu is relatively restricted as compared to the brain, thereby facilitating the tracing of migratory behavior of cells and their processes. Previous studies in the Appel laboratory demonstrated that the olig2 gene is necessary for formation of OPC and spinal motor neurons from the pMN domain of the zebrafish spinal cord. Because oligodendrocytes are present throughout the central nervous system, they extended this hypothesis along the anterior axis to the hindbrain.

Using elegant transgenic strategies and lineage-specific antibody labeling, Zannino et al. first characterized neuronal and glial cells in the hindbrain. They witnessed olig2 mRNA expression specifically in rhombomeres 5 and 6 (r5/r6) of the hindbrain, which was corroborated by enhanced green fluorescent protein (GFP) driven by olig2 regulatory DNA in transgenic embryos: Tg(olig2:eGFP). Antibody staining for Zn8, a marker for somatic abducens motor neurons, was also specific for the 5th and 6th rhombomeres, unlike the broad motor neuron marker, Isl1. Thus hindbrain abducens motor neurons and some OPCs may be specified from a common precursor population. Through time-lapse imaging of Tg(olig2:eGFP) embryos, they next demonstrated that OPCs come from within neuroepithelial precursors in the 5th and 6th rhombomeres of the hindbrain, but that many also arise from olig2- precursors elsewhere in the hindbrain.

The investigators next show that the knockdown of the olig2 gene by targeted antisense morpholino (MO) resulted in a specific effect on hindbrain cells. In morpholino-injected embryos, olig2 RNA expression was maintained in rhombomeres r5 and r6; however, these cells appeared abnormal at 48 hours post-fertilization, in that most cells appeared to be undifferentiated neuroepithelial precursors and did not possess abducens morphologies. Additionally, BrdU staining for mitotically active cells continued in the hindbrain of MO-injected embryos long after control siblings, suggesting that these cells remain in an undifferentiated state. These results suggest that Olig2 function is necessary for formation of both hindbrain OPCs and somatic abducens motor neurons.