LOCALIZED WNT3A-SOURCES INSTRUCT MITOTIC ORIENTATION: DISSECTING THE WNT3A-TRANSDUCTION MECHANISM COUPLED WITH NUMA MACHINERY
type: CreativeWork
description: In multicellular organisms, morphogenesis and homeostasis of epithelial tissues require oriented cell divisions, which rely on the proper positioning of the mitotic spindle. Consistently, defects in epithelial polarity and spindle orientation are often coupled with loss of tissue architecture and altered proliferation. Since mitotic spindle orientation determines the axis of cell division, in stem cells it plays a pivotal role in the symmetric or asymmetric fate acquired by the daughter cells after cytokinesis. During asymmetric cell division, the spindle aligns parallel to the polarity axis to ensure asymmetric inheritance of cell fate determinants and to expose daughter cells to different niche microenvironment. Mechanistically, microtubules (MTs) motors and actin regulators have been implicated in the response to extracellular cues that instruct the orientation of the division by binding to adhesion molecules including cadherins and integrins, or to players of diverse signalling pathways. The synergistic link between the external and internal cues instructing division orientation converge on the evolutionary conserved pathway consisting of dynein/NuMA/LGN/Gai cortical complexes that define the spindle alignment by exerting pulling forces on dynamic plus-ends of astral MTs to control spindle position and orientation. How these force generators respond to extracellular signal remains poorly characterised. In numerous stem cells niches, Wnt ligands assume a restricted spatial localisation that contribute to regulate the mitotic spindle alignment toward the niche. However how cells sense Wnt signals to orient the division axis is largely unknown. A major goal of my PhD project was to dissect genetically and biochemically the mechanism that transduce localised Wnt3a signals to the spindle apparatus during mitosis in order to instruct division orientation. Live-cell imaging experiments conducted in HeLa cells dividing in contact with an in vitro niche system such as Wn…
abstract: In multicellular organisms, morphogenesis and homeostasis of epithelial tissues require oriented cell divisions, which rely on the proper positioning of the mitotic spindle. Consistently, defects in epithelial polarity and spindle orientation are often coupled with loss of tissue architecture and altered proliferation. Since mitotic spindle orientation determines the axis of cell division, in stem cells it plays a pivotal role in the symmetric or asymmetric fate acquired by the daughter cells after cytokinesis. During asymmetric cell division, the spindle aligns parallel to the polarity axis to ensure asymmetric inheritance of cell fate determinants and to expose daughter cells to different niche microenvironment. Mechanistically, microtubules (MTs) motors and actin regulators have been implicated in the response to extracellular cues that instruct the orientation of the division by binding to adhesion molecules including cadherins and integrins, or to players of diverse signalling pathways. The synergistic link between the external and internal cues instructing division orientation converge on the evolutionary conserved pathway consisting of dynein/NuMA/LGN/Gai cortical complexes that define the spindle alignment by exerting pulling forces on dynamic plus-ends of astral MTs to control spindle position and orientation. How these force generators respond to extracellular signal remains poorly characterised. In numerous stem cells niches, Wnt ligands assume a restricted spatial localisation that contribute to regulate the mitotic spindle alignment toward the niche. However how cells sense Wnt signals to orient the division axis is largely unknown. A major goal of my PhD project was to dissect genetically and biochemically the mechanism that transduce localised Wnt3a signals to the spindle apparatus during mitosis in order to instruct division orientation. Live-cell imaging experiments conducted in HeLa cells dividing in contact with an in vitro niche system such as Wn…
author: ELI, SUSANNA
language: eng
keywords: Oriented cell division, Wnt, Mitotic spindle, Settore BIO/10 - Biochimica
date published: 2023-04-13
date modified: 2026-07-27T20:18:58Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/957722

PropertyValue
property ID: DOI
value: 10.13130/eli-susanna_phd2023-04-13