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Project Overview

Function of IMD-proteins in neuronal development and maturation

A wide range of cell biological processes including cell division, motility and morphogenesis depend on the dynamic and locally specific regulation of the actin cytoskeleton. One central group of proteins functioning at the interface between signaling and the actin cytoskeleton are metastasis suppressor 1 (Mtss1, also known as MIM), insulin receptor substrate p53 (IRSp53, also known as BAIAP2), ABBA (Mtss1L), IRTKS (BAIAP2L1) and FLJ22582 (BAIAP2L2).
Recently, we could show that Mtss1 expression is developmentally downregulated in cerebellar granule cells, whereas expression in Purkinje cells persists throughout differentiation. Furthermore, neuronal maturation of the cerebellum is accompanied by a switch in Mtss1 splicing: A Mtss1 variant also observed in peripheral tissues and comprising exon 12 is replaced by the CNS-specific isoform containing exon 12a. Bioinformatic analysis of Mtss1 suggests that differential exon usage may affect interaction with Fyn and Src, two tyrosine kinases previously recognized as critical for cerebellar cell migration and histogenesis (Glassmann et al., 2007). We aim to unravel the role of Mtss1 and its homologues for cytoskeletal dynamics in developing and mature cerebellar neurons using various genetic and cell biological approaches as well as advanced microscopic techniques.

Regulation of cerebellar development by microRNA-mediated processes MicroRNAs

are a class of post-transcriptional regulators. They are short ~22 nucleotide RNA sequences that bind to complementary sequences in the 3' UTR of multiple target mRNAs, usually resulting in their silencing. MicroRNAs are abundant in the nervous system, where they have key roles in development and are likely to be important mediators of plasticity.
We identified several microRNA species that are differentially regulated in the maturing cerebellum. We now aim to elucidate the nature and function of their targets by a variety of biochemical, cell biological, and genetic methods.

Publications by Dr. Eiberger