egr2cre mediated conditional ablation of dicer disrupts histogenesis of mammalian central auditory nucleiegr2cre介导条件消融的帽子会破坏组织发生的哺乳动物的中枢听觉核.pdfVIP

Egr2::Cre Mediated Conditional Ablation of Dicer Disrupts Histogenesis of Mammalian Central Auditory Nuclei 1 1 1 2 Elena Rosengauer , Heiner Hartwich , Anna Maria Hartmann , Anya Rudnicki , Somisetty 1 2 1,3 Venkata Satheesh , Karen B. Avraham , Hans Gerd Nothwang * 1 Department of Neurogenetics, Carl von Ossietzky University Oldenburg, Oldenburg, Germany, 2 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 3 Center for Neuroscience, Carl von Ossietzky University Oldenburg, Oldenburg, Germany Abstract Histogenesis of the auditory system requires extensive molecular orchestration. Recently, Dicer1, an essential gene for generation of microRNAs, and miR-96 were shown to be important for development of the peripheral auditory system. Here, we investigated their role for the formation of the auditory brainstem. Egr2::Cre-mediated early embryonic ablation of Dicer1 caused severe disruption of auditory brainstem structures. In adult animals, the volume of the cochlear nucleus complex (CNC) was reduced by 73.5%. This decrease is in part attributed to the lack of the microneuronal shell. In contrast, fusiform cells, which similar to the granular cells of the microneural shell are derived from Egr2 positive cells, were still present. The volume reduction of the CNC was already present at birth (67.2% decrease). The superior olivary complex was also drastically affected in these mice. Nissl staining as well as Vglut1 and Calbindin 1 immunolabeling revealed that principal SOC nuclei such as the