Identification of proliferative progenitors associated with prominent postnatal growth of the pons

Abstract

The pons controls crucial sensorimotor and autonomic functions. In humans, it grows sixfold postnatally and is a site of paediatric gliomas; however, the mechanisms of pontine growth remain poorly understood. We show that the murine pons quadruples in volume postnatally; growth is fastest during postnatal days 0–4 (P0–P4), preceding most myelination. We identify three postnatal proliferative compartments: ventricular, midline and parenchymal. We find no evidence of postnatal neurogenesis in the pons, but each progenitor compartment produces new astroglia and oligodendroglia; the latter expand 10- to 18-fold postnatally, and are derived mostly from the parenchyma. Nearly all parenchymal progenitors at P4 are Sox2+Olig2+, but by P8 a Sox2− subpopulation emerges, suggesting a lineage progression from Sox2+ ‘early' to Sox2− ‘late' oligodendrocyte progenitor. Fate mapping reveals that >90% of adult oligodendrocytes derive from P2–P3 Sox2+ progenitors. These results demonstrate the importance of postnatal Sox2+Olig2+ progenitors in pontine growth and oligodendrogenesis.

Regional oligodendrocytopathy and astrocytopathy precede myelin loss and blood–brain barrier disruption in a murine model of osmotic demyelination syndrome

“…For instance, in ODS rat model, demyelinating lesions were rarely identified in the pons, although they are found in human patients and in the mouse model. This observation could be explained by comparable cyto-and myelo-architectures of murine and human pons, composed of an admixture of grey and white matters (Lindquist et al, 2016).…”

“…Relative analysis of Cx47 mRNA was not significantly changed despite a trend toward diminution at 24 hr after the correction (d). This observation could be explained by comparable cyto-and myelo-architectures of murine and human pons, composed of an admixture of grey and white matters (Lindquist et al, 2016). The quantification of Cx43 immunoreactivity showed a significant reduction at 48 hr after the correction, while a non-statistically diminution was already observed at 24 hr after the correction (f).…”

Histone H3.3 K27M Accelerates Spontaneous Brainstem Glioma and Drives Restricted Changes in Bivalent Gene Expression

“…We induced genetically engineered mutations in Nestin-positive cells in neonatal mice to coincide with the developmental period when most gliogenesis occurs, including the period of greatest postnatal growth in the pons, from P0 to P4 (Lindquist et al, 2016). A recent study using neonatal in vivo electroporation to introduce H3.3 K27M combined with p53 knockdown failed to induce tumors, while in utero electroporation to overexpress H3.3 K27M with CRISPR/Cas9-mediated Trp53 deletion induced gliomas (Pathania et al, 2017).…”

Brainstem development requires galactosylceramidase and is critical for the pathogenesis of Krabbe Disease

“…6d, e). The murine pons, which is a core structure of brainstem, quadruples in volume shortly after birth and peaks at P4, preceding myelination 36 . During this period, postnatal SOX2+Olig2+ OL-progenitor cells (OPC) expand 10-18 fold into the OL-lineage cells that later comprise the more than 90% of adult pons OLs.…”

“…Similarly, postnatal refinement of neurons of the visual cortex is critical for the intrinsic properties and plasticity needed for proper function and network activity 47 . Furthermore, most pontine circuits are postnatally acquired or refined 36 , which contains nuclei that relay signals from the forebrain to the cerebellum, along with nuclei that deal primarily with vital functions 48 . Therefore, our finding that GALC influences postnatal neuronal differentiation, while surprising, is not unprecedented.…”