NeuroanatomyPurkinje cell subtype specification in the cerebellar cortex: Early B-cell factor 2 acts to repress the zebrin II-positive Purkinje cell phenotype
Section snippets
Mice
All animal procedures conformed to institutional regulations and the Guide of the Care and Use of Experimental Animals from the Canadian Council of Animal Care. All experiments conformed to international guidelines on the ethical use of animals. Every effort was made to minimize the number of animals used and their suffering. The targeting construct, described in Corradi et al. (2003), contained a lacZ cDNA and the distribution of lacZ expression during CNS development is in full agreement with
Results
There are two distinct abnormalities in the Ebf2 null cerebellum. First, ectopic gene expression in the zebrin II−/PLCβ4+ population reveals a partial phenotype transdifferentiation from P− to P+. Secondly, the stripe pattern is not normal, and we will argue below that this is likely due to both ectopic gene expression and selective Purkinje cell death (see also Croci et al., 2006). The degree to which each of these effects is observed depends on the particular transverse zone.
Discussion
In this study, we have further characterized the role of Ebf2 in the development of cerebellar topography. The new findings are (i) Ebf2 gene deletion results in the ectopic expression of several characteristic P+ Purkinje cell markers in P− Purkinje cells; (ii) abnormal cerebellar topography in Ebf2 null mice differs between transverse zones: selective Purkinje cell death occurs in the PZ and AZ vermis, but not in the CZ and NZ vermis, and ectopic gene expression occurs in the PZ hemisphere
Acknowledgments
These studies were supported by grants from the Canadian Institutes of Health Research (R.H.), and the CARIPLO foundation (G.G.C.).
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2021, NeuroscienceCitation Excerpt :More recent studies have confirmed that cellular birthdate and embryonic identity correlate with molecular identity in the mature cerebellum: early- and late-born cells become ZebrinII-negative and ZebrinII-positive Purkinje cells, respectively (Hashimoto and Mikoshiba, 2003; Sillitoe et al., 2009; Namba et al., 2011). There is evidence that the transcription factor Ebf2 plays a role in early Purkinje cell differentiation, with Ebf2 repressing ZebrinII-identity (Chung et al., 2008). After Purkinje cell identity is established, they initiate expression of different markers.
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