Role of Transcription Factor Zbtb20 in Developing Cerebellum of Rodents: Regulation of Purkinje Cells Generation and Distribution

Development of cerebellum is a compound process, taking place pre- and postnatally. It is governed by multiple intra- and extracellular factors. Many studies have revealed the molecular mechanisms regulating different aspects of cerebellar development and related pathological entities. However, our understanding about certain factors modulating cerebellar development is still insufficient. Natural mutants and genetically engineered animal models allow to target particular gene products and to understand their role. Therefore, we performed experiments on homozygous knockout mice (Zbtb20-/-) and wild-type animals (controls) to examined the effect of transcription factor Zbtb20 on Purkinje cells (PCs) development during the early postnatal (P) stages – days 4, 8, and 12. Parasagital sections were treated immunocytochemically with antibody against the PCs’ marker Calbindin. Zbtb20 showed time- and space-differential effect: on P4, the lack of Zbtb20 resulted in total upregulation of PCs number, and selectively in folia 3, 8, 9 and 10; on P8 only folium 3 and 10 in the mutants had higher PCs number, while on P12 the opposite was observed – lower PCs’ number in the mutants. Additionally, a difference in the Pcs’ dendritic arborization was detected in Zbtb20-/-. To the best of our knowledge, this is the first study on the role of Zbtb20 on early postnatal PCs development. These findings provide new insights to the cerebelar development, and could have a significant clinical relevance.