Early cerebellar granule cell migration in the mouse embryonic development

Abstract

Pax6, a paired homeobox DNA binding protein, has been found to be expressed in the cerebellum in both granule cells and their precursors in the external granular layer (EGL). In this study we have traced Pax6 expression through embryonic development in mice by using a polyclonal antibody against Pax6 and used it to study the cellular dispersal pattern of the EGL. During dispersal the EGL was thicker and Pax6 expression was more intense on the rostral side of the lateral corners of the cerebellum. Pax6 immunoreactive cells were found to be migrating from the EGL during the early stage of EGL dispersal, which suggested the early inward migration of granule cells. Double staining with various markers confirmed that the early-migrating cells are not Purkinje cells, interneurons or glia. Although the Pax6 immunoreactive cells within the cerebellum were not apparently proliferating, NeuN, a marker for postmitotic granule cells, was not expressed in these cells until E16. Furthermore, granule cells were observed migrating inwards from the EGL both during and after EGL dispersal. These early migrating granule cells populated the whole cerebellum. These findings offer novel views on specific stages of granule cell dispersal and migration.

The Human Protein Atlas as a proteomic resource for biomarker discovery

“…2c,j). These data are in agreement with previously reported results of Pax6 expression in tissues such as the pancreas and cerebellum [31–33].…”

Cux2 serves as a novel lineage marker of granule cell layer neurons from the rhombic lip in mouse and chick embryos

“…However, dosing the Cux2 CreERT2 :Rosa26 tdTomato mice at E10.5 resulted in very low (if any) co‐labeling with either of these factors. In fact, the majority of tomato‐labeled cells in these animals co‐expressed Pax6 and were found in the EGL, consistent with restricted labeling of GCL precursors (Engelkamp et al, ; Chung et al, ). Of interest, it is thought that GCs are not yet being generated at E11–12, but rather begin being born around E12.5 (Machold and Fishell, ).…”

“…In addition, at E16.5, GCs begin to express NeuN as they migrate deeper to form the GCL (Chung et al, ), accounting for the increased co‐expression of NeuN in Cux2‐Cre driven tomato‐positive cells observed at E12.5 vs. E10.5 labeling. Furthermore, because Pax6 is down‐regulated in DCN neurons beginning before E16.5 (Fink et al, ), the co‐labeling of tomato‐positive cells with Pax6 in the EGL and Tbr2 confirmed that they were exclusively GCs or UBCs, respectively.…”

Postnatal developmental profile of neurons and glia in motor nuclei of the brainstem and spinal cord, and its comparison with organotypic slice cultures

“…The organotypic cultures prepared with embryonic spinal tissue produced very low immunoreactivity for neurons up to 7 DIV. Lack of NeuN immunoreactivity at 2 DIV was probably due to the insufficient expression of this protein by the embryonic tissue (Chung et al,2010) rather than axotomy‐induced loss of NeuN signal which is a functional response of damaged neurons in the adult spinal cord (McPhail etal.,2004).…”