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Published on: June 13, 2020
Identification of proliferative progenitors associated with prominent postnatal growth of the pons
Robert A Lindquist1,2,3, Cristina D Guinto1,4, Jose L Rodas-Rodriguez1,4
1Eli &Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California-San Francisco, San Francisco, California 94143, USA.
Insights
Postnatal pontine growth involves specific progenitor cells, not new neurons. Sox2(+)Olig2(+) progenitors are key drivers of pontine growth and oligodendrocyte production in early development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- The pons is vital for sensorimotor and autonomic functions.
- Pontine growth mechanisms and pediatric glioma origins are poorly understood.
- Human pons grow sixfold postnatally, while murine pons quadruple.
Purpose of the Study:
- To investigate the mechanisms of postnatal pontine growth.
- To identify progenitor cells responsible for pontine development.
- To understand oligodendrocyte development in the postnatal pons.
Main Methods:
- Murine model for studying postnatal brain development.
- Analysis of proliferative compartments (ventricular, midline, parenchymal).
- Cell lineage tracing and progenitor marker analysis (Sox2, Olig2).
Main Results:
- Pontine growth is rapid between postnatal days 0-4, preceding myelination.
- Three proliferative compartments identified: ventricular, midline, and parenchymal.
- Oligodendrocytes expand 10-18 fold, primarily from parenchymal progenitors.
- Postnatal neurogenesis is absent; astroglia and oligodendroglia are produced.
- A lineage progression from Sox2(+) to Sox2(-) oligodendrocyte progenitors was observed.
- Over 90% of adult oligodendrocytes originate from early postnatal Sox2(+) progenitors.
Conclusions:
- Postnatal pontine growth relies on specific progenitor compartments, not neurogenesis.
- Sox2(+)Olig2(+) progenitors are crucial for pontine growth and oligodendrogenesis.
- Understanding these mechanisms may inform pediatric glioma research.
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.
