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Regulation of microtubule-organizing centers during development in Drosophila melanogaster
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Resumo(s)
The organization of the microtubule (MT) cytoskeleton is essential for many cellular functions,
including cell shape, polarity, migration, and division. The geometry of MT networks critically depends
on the localization of sites called microtubule organizing centers (MTOCs), which contain proteins that
promote MT nucleation, anchoring, and/or stabilization. The best-studied MTOC is the centrosome,
composed of two MT-based centrioles, surrounded by the pericentriolar material (PCM). The PCM is
a multicloud of proteins essential for the activity of the centrosome as an MTOC. However, upon mitotic
exit or cell differentiation, the activity of the centrosome as an MTOC is generally attenuated and in
extreme cases, it can be eliminated. This is often associated with the remodeling of the MT cytoskeleton
into cell-type specific MT arrays with the assignment of MTOC function to other places in the cell,
named non-centrosomal MTOCs (ncMTOCs). In contrast to centrosomes, we know very little about the
composition, structure, and function of ncMTOCs. We set ourselves to investigate how ncMTOCs are
assembled and regulated by using the Drosophila germline as a model. I found that upon centrosomal
inactivation both in oocytes and follicular cells, the centrosomal MT regulator WDR-62 becomes
localized at ncMTOCs. I performed functional studies in the oocytes, which strongly suggest that WDR62 is required for the organization of the MT cytoskeleton. I also found that WDR-62, as well as the
conserved ncMTOC component, Shot, are interdependent for their localization at the ncMTOCs. This
suggests WDR-62 is a core ncMTOC component. We are currently investigating the role of WDR-62
at ncMTOCs. Wdr62 is the second most common genetic cause of microcephaly in human patients.
Therefore, understanding the role of this protein not only in centrosomes but also at ncMTOCs might
lead to important insight into its relevance, in normal development but also disease.
Descrição
Tese de mestrado, Biologia Molecular e Genética, 2023, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
WD repeat-containing protein 62 (WDR-62) MTOCs não-centrossomais Drosophila melanogaster Oogénese Teses de mestrado - 2023