Abstract
In the developing cerebellum, the nascent white matter (WM) serves as an instructive niche for cerebellar cortical inhibitory interneurons. As their Pax2 expressing precursors transit the emerging WM, their laminar fate is programmed. The source(s) and nature of the signals involved remain unknown. Here, we used immunocytochemistry to follow the cellular maturation of the murine cerebellar WM during this critical period. During the first few days of postnatal development, when most Pax2 expressing cells are formed and many of them reach the cerebellar gray matter, only microglial cells can be identified in the territories through which Pax2 cells migrate. From p4 onward, cells expressing the oligodendrocytic or astrocyte markers, CNP-1, MBP or GFAP, started to appear in the nascent WM. Expression of macroglial markers increased with cerebellar differentiation, yet deep nuclei remained GFAP-negative at all ages. The progressive spread of maturing glia did not correlate with the exit of Pax2 cells from the WM, as indicated by the extensive mingling of these cells up to p15. Whereas sonic hedgehog-associated p75NTR expression could be verified in granule cell precursors, postmitotic Pax2 cells are p75NTR negative at all ages analyzed. Thus, if Pax2 cells, like their precursors, are sensitive to sonic hedgehog, this does not affect their expression of p75NTR. Our findings document that subsequently generated sets of Pax2 expressing precursors of inhibitory cerebellar interneurons are confronted with a dynamically changing complement of cerebellar glia. The eventual identification of fate-defining pathways should profit from the covariation with glial maturation predicted by the present findings.
Highlights
The cerebellum is derived from two major germinative layers, both of which originate from the dorso-rostral neuroepithelium lining the fourth ventricle
These findings led to the view that within the deep cerebellar mass and nascent white matter (WM) of Cerebellum (2020) 19:286–308 the cerebellar anlage, precursors of inhibitory cerebellar interneurons are confronted with signals that regulate their numeric expansion and program their final phenotypic differentiation [12, 13]
While the external granule cell layer (EGL) is again devoid of Pax2 cells, many of them can be found throughout the nascent white matter (WM) and again within the velum medullare
Summary
The cerebellum is derived from two major germinative layers, both of which originate from the dorso-rostral neuroepithelium lining the fourth ventricle (for a recent review and further references, see [1]). Rather, transplanted cells developed into exactly those types of GABAergic interneurons that were formed by hosts cells transiting the prospective white matter at the time of transplantation [10; see 7]. Together, these findings led to the view that within the deep cerebellar mass and nascent white matter (WM) of Cerebellum (2020) 19:286–308 the cerebellar anlage, precursors of inhibitory cerebellar interneurons are confronted with signals that regulate their numeric expansion and program their final phenotypic differentiation [12, 13]
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