Developmental fates and migratory pathways of dividing progenitors in the postnatal rat cerebellum

Abstract

To investigate the developmental fates and the migratory pathways of dividing progenitors in both the white matter (WM) and the external granule layer (EGL) in the early postnatal rat cerebellum, a replication-deficient retrovirus carrying the beta-galactosidase gene (BAG) was injected into the deep cerebellar tissue or the EGL of postnatal rats to label dividing progenitors. After 1-3 days post-injection (1-3 dpi) of BAG into the deep cerebellar tissue of postnatal day 4/5 (P4/5) rats, labeled immature, unipolar cells were found mainly in the WM. From 4 to 6 dpi, similar cells appeared in the internal granule (IGL), Purkinje cell, and molecular layers, although about half of the labeled cells still resided in the WM and appeared immature. The first morphologically definable Bergmann glia, astrocytes, and oligodendrocytes were also observed. From 14 to 20 dpi, most labeled cells had developed into Bergmann glia, astrocytes, oligodendrocytes, and interneurons in their appropriate layers. When BAG injections were performed at P14, unipolar cells were initially observed, but the majority of these differentiated into myelinating oligodendrocytes in the WM and IGL by 17 dpi. Few immature cells were labeled by injections administered at P20, and these did not develop into mature glia, but into cells with lacy, fine processes, possible representing immature oligodendrocytes. In contrast, BAG-labeled progenitors of EGL produced only granule neurons. Thus, within the first 2 postnatal weeks, dividing progenitors in the WM migrate as immature cells into the cortex before differentiating into a variety of glia and interneurons. The genesis of oligodendrocytes continues through the 2nd postnatal week and largely ceases by P20. EGL cells do not produce glia, but only granule cells.

Neurogenin1 expression in cell lineages of the cerebellar cortex in embryonic and postnatal mice

“…Migrating cells in the WM of the postnatal cerebellum are known to include mitotically active GABAergic interneuron precursors (Zhang and Goldman, 1996a;Maricich and Herrup, 1999). We examined the cell lineage and mitotic profile of postnatal Ngn1-expressing cells by anti-Ptf1a and BrdU pulse-immunolabeling.…”

Cerebellar granule cell precursors can differentiate into astroglial cells

“…Recent studies, however, using quail-chick chimeras (28,29), transplantation of EGL cells (30), or retroviral labeling of EGL cells (31,32) indicate that cells in the EGL give rise to granule cells exclusively in vivo. Here, we show that some EGL GCPs can differentiate into GFAP-positive glial cells in vitro also.…”

“…We cannot completely exclude the possibility that the induced GFAP-positive cells could have developed from the progenitors in the white matter of the cerebellum, which are reported to give rise to cortical interneurons (stellate cells and basket cells in the molecular layer and Golgi cells in the GL), astroglial cells, and oligodendrocytes (31,32). We think that the possibility is unlikely, however, for the following two reasons.…”

Heterogeneity and Bipotency of Astroglial-Like Cerebellar Progenitors along the Interneuron and Glial Lineages

“…Although the EGL exclusively produces granule neurons (Hallonet et al, 1990;Alvarez-Otero et al, 1993), the PWM comprises cells belonging to the interneuronal, astroglial, and oligodendroglial lineages (Leto et al, 2012). The PCL instead hosts a subset of postmitotic Bergmann glia (BG) and precursors for this astroglial type (Yamada and Watanabe, 2002;Sudarov et al, 2011;Buffo and Rossi, 2013). However, a neurogenic potential has also been hypothesized for PCL-residing progenitors (Alcock et al, 2007;Alcock and Sottile 2009).…”