Functional characterization of a novel basal body/centrosomal protein

• Antragsteller: Professor Dr. Achim Gossler
• Fachliche Zuordnung: Entwicklungsbiologie
• Förderung: Förderung von 2012 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 218553926

Cilia are dynamic cellular projections formed by stereotypically arranged microtubules that originate at a cortically located basal body, a centriolar structure that acts as a microtubule organizing center. Cilia have essential functions and defects in cilia or basal body formation, structure and function disrupt normal development and tissue homeostasis, and underlie various human diseases that are collectively referred to as ciliopathies. Likewise, abnormal centrosome biogenesis can lead to amplification of centrioles and supernumerary centrosomes, which in turn can lead to multipolar spindles, chromosome misseggregation and aneuploidy. We have identified the homeobox transcription factor NOTO as a pivotal regulator of ciliogenesis in early mouse embryos. Genes regulated by NOTO encode cilia components with known functions as well as proteins with unknown function that are present in the known ciliary proteome. Thus, genes regulated by NOTO are good candidates for novel components important for cilia/basal body formation and function. One of these genes referred to as M57 codes for a novel basal body/ centrosomal protein. Knock-down of M57 causes over-duplication of centrosomes suggesting that M57 is involved in the regulation of centriole biogenesis. We propose to comprehensively study M57 with respect to its biochemical, cellular and physiological functions to understand its mechanism of function and significance in the centrosome cycle.

• DFG-Verfahren: Sachbeihilfen