Anat Cell Biol.  2010 Mar;43(1):72-77. 10.5115/acb.2010.43.1.72.

TBR2-immunopsitive unipolar brush cells are associated with ectopic zebrin II-immunoreactive Purkinje cell clusters in the cerebellum of scrambler mice

• Chung SH
• Kim CT
• Jeong YG
• Lee NS

• KMID: 2168899
• DOI: http://doi.org/10.5115/acb.2010.43.1.72

Abstract

Unipolar brush cells (UBCs) are excitatory interneurons with their somata located in the granular layer. Recently, T-brain factor 2 (Tbr2) was shown to be expressed in a subset of UBCs in mouse cerebellum. Scrambler mice exhibit severe cerebellum abnormalities, including the failure of embryonic Purkinje cell dispersal and a complete absence of foliation due to a mutation in the disabled-1 adaptor protein. Since most UBC markers are expressed postnatally, it has proven difficult to identify the relationship between developing Purkinje cell clusters and migrating UBCs. Because scrambler mice closely mimic normal embryonic day 18 cerebellum, we examined whether Tbr2-positive UBCs are associated with Purkinje cell cluster markers such as zebrin II, which is the most studied compartmentation marker in the cerebellum. We investigated the distribution of Tbr2-positive UBCs in this mutant by using anti-Tbr2 immunocytochemistry. The data revealed that Tbr2 immunoreactivity was exclusively present in the nucleus of UBCs in scrambler cerebellum. Based on expression data, a Tbr2-positive UBC map was constructed. In addition, Tbr2-positive UBCs are found associated with ectopic zebrin II-immunoreactive Purkinje cell clusters in scrambler cerebellum. These data suggest that UBCs use Purkinje cell compartmentation to migrate into their final position through interactions with the embryonic array of specific Purkinje cell subtypes.

Keyword

Tbr2; unipolar brush cell; scrambler; zebrin; cerebellum

MeSH Terms

Animals
Cell Compartmentation
Cerebellum
Hydrazines
Immunohistochemistry
Interneurons
Mice
Nerve Tissue Proteins
Hydrazines
Nerve Tissue Proteins

Figure

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  Fig. 1 Unipolar brush cells (UBCs) express Tbr2 in the cerebellum of scrambler mice. Transverse scrambler cerebellum section through the posterior lobe vermis immunoperoxidase stained with anti-Tbr2. Very strong immunoperoxidase products were deposited in individual cells. Tbr2 immunoreactivity is exclusively detected in the nucleus of UBCs. No other structures are stained. The rectangular layer is demonstrated with high-power image in inlet. Midline is indicated by a dotted line. Scale bar = 125 µm.

• 

  Fig. 2 Serial reconstruction of the distribution of Tbr2-immunoreactive UBCs in scrambler mutant mice. (A) In posterior cerebellum, Tbr2-immunoreactive UBCs are mainly located in the ventral part of the vermis. (B~C) Middle and anterior part of the scrambler cerebellum. Tbr2-positive UBCs are present in the vermis and hemisphere region. Scale bar = 500 µm.

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  Fig. 3 A subset of Tbr2-immunoreactive UBCs is aligned with the zebrin II subset of Purkinje cells in the scrambler cerebellum. (A~C) Double immunofluorescence staining with anti-zebrin II and Tbr2 shows that ectopic Purkinje cells within the cerebellum express both zebrin II (green) and Tbr2 in scrambler vermis. (D~F) In Scrambler hemisphere, clusters of Tbr2-immunoreactive UBCs (red) are topographically aligned with a subset of zebrin II-immunoreactive Purkinje cells (green). Scale bar = 100 µm.

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