Proliferation Of Glial Precursors Research Articles

Transcriptional Regulator ZEB2 Is Essential for Bergmann Glia Development.

Bergmann glia facilitate granule neuron migration during development and maintain the cerebellar organization and functional integrity. At present, molecular control of Bergmann glia specification from cerebellar radial glia is not fully understood. In this report, we show that ZEB2 (aka, SIP1 or ZFHX1B), a Mowat-Wilson syndrome-associated transcriptional regulator, is highly expressed in Bergmann glia, but hardly detectable in astrocytes in the cerebellum. The mice lacking Zeb2 in cerebellar radial glia exhibit severe deficits in Bergmann glia specification, and develop cerebellar cortical lamination dysgenesis and locomotion defects. In developing Zeb2-mutant cerebella, inward migration of granule neuron progenitors is compromised, the proliferation of glial precursors is reduced, and radial glia fail to differentiate into Bergmann glia in the Purkinje cell layer. In contrast, Zeb2 ablation in granule neuron precursors or oligodendrocyte progenitors does not affect Bergmann glia formation, despite myelination deficits caused by Zeb2 mutation in the oligodendrocyte lineage. Transcriptome profiling identified that ZEB2 regulates a set of Bergmann glia-related genes and FGF, NOTCH, and TGFβ/BMP signaling pathway components. Our data reveal that ZEB2 acts as an integral regulator of Bergmann glia formation ensuring maintenance of cerebellar integrity, suggesting that ZEB2 dysfunction in Bergmann gliogenesis might contribute to motor deficits in Mowat-Wilson syndrome.SIGNIFICANCE STATEMENT Bergmann glia are essential for proper cerebellar organization and functional circuitry, however, the molecular mechanisms that control the specification of Bergmann glia remain elusive. Here, we show that transcriptional factor ZEB2 is highly expressed in mature Bergmann glia, but not in cerebellar astrocytes. The mice lacking Zeb2 in cerebellar radial glia, but not oligodendrocyte progenitors or granular neuron progenitors, exhibit severe defects in Bergmann glia formation. The orderly radial scaffolding formed by Bergmann glial fibers critical for cerebellar lamination was not established in Zeb2 mutants, displaying motor behavior deficits. This finding demonstrates a previously unrecognized critical role for ZEB2 in Bergmann glia specification, and points to an important contribution of ZEB2 dysfunction to cerebellar motor disorders in Mowat-Wilson syndrome.

Proliferation of glial precursors during the early development of the chick optic nerve.

The mitotic patterns and cytoarchitecture of the optic stalk were studied in the chick embryo during the period of formation of the optic cup until the elimination of the stalk lumen. Cell proliferation in the superficial regions of the stalk ventral wall is described. Superficial cell proliferation, whose beginning coincides with penetration of the earliest optic fibers, gives rise to an early glioblast plate located internally with respect to the marginal lamina of ganglion cell axon fascicles. The early glioblasts are transformed into marginal glioblasts, which undergo radial mitosis. Radially oriented division seems to favour glioblast penetration towards more internal zones of the stalk. Thus the marginal glioblasts are transformed into inner glioblasts, which continue to proliferate. Cell death in the ventral wall of the optic stalk is in close topographical relation with extracellular spaces which loosen up the consistency of the stalk tissue, favouring invasion of the ventral stalk by optic fibers and the addition of new glioblasts by proliferation of preexisting cells.

Radioautographic evidence for the protracted proliferation of glial cells in the central nervous system of jimpy mice

Proliferation of glial cells has been studied in the central nervous system of jimpy mice and control littermates with [ 3H]thymidine radioautography. It was found that the proliferation of glial precursors was protracted in the 3 regions studied: spinal cord, cerebellum and corpus callosum. The difference between jimpy and littermates became obvious in each of these regions at the onset of myelination. It is concluded that the maturation of the oligodendrocyte is the target of the mutation. The protracted proliferation of glioblasts is a consequence of the absence of stable interactions with the axons.