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Gonczy, P.

Publications and source records attributed to Gonczy, P..

3 recordsLinked to original sources

Aurora A depletion reveals centrosome-independent polarization mechanism in C. elegans

How living systems break symmetry in an organized manner is an important question in biology. In C. elegans zygotes, symmetry breaking normally occurs in the vicinity of centrosomes, resulting in anterior-directed cortical flows and establishment of a single posterior PAR-2 domain. Here, we report that zygotes depleted of the Aurora A kinase AIR-1 or of centrosomes establish two posterior domains, one at each pole. Using transgenic animals and microfabricated triangular chambers, we establish that such bipolarity occurs in a PAR-2- and curvature-dependent manner. Furthermore, we develop an integrated physical model of symmetry breaking, establishing that local PAR-dependent weakening of the actin cortex, together with mutual inhibition of anterior and posterior PAR proteins, provides a mechanism for self-organized PAR polarization without functional centrosomes in C. elegans.\n\nOne Sentence SummaryWe uncover a novel centrosome-independent mechanism of polarization in C. elegans zygotes

cell biology

Multicolor single particle reconstruction of protein complexes

Single-particle reconstruction (SPR) from electron microscopy images is widely used in structural biology, but lacks direct information on protein identity. To address this limitation, we developed a computational and analytical framework that reconstructs and co-aligns multiple proteins from 2D super-resolution fluorescence images. We demonstrate our method by generating multi-color 3D reconstructions of several proteins within the human centriole and procentriole, revealing their relative locations, dimensions and orientations.

cell biology

PI(4,5)P2 forms dynamic cortical structures and directs actin distribution and cell polarity in C. elegans embryos

Asymmetric division is crucial for embryonic development and stem cell lineages. In the one-cell C. elegans embryo, a contractile cortical actomyosin network contributes to anterior-posterior (A-P) polarity and asymmetric division by segregating PAR proteins to discrete cortical domains. Here, we discovered that the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) forms dynamic structures in C. elegans zygotes, distributing in a polarized and PAR-dependent manner along the A-P axis. PIP2 cortical structures overlap with F-actin and coincide with the actin regulators RHO-1, CDC-42 and ECT-2. Particle image velocimetry analysis revealed that PIP2 and F-actin cortical movements are coupled, with PIP2 structures moving slightly ahead. Importantly, we established that PIP2 cortical structures form in an actin-dependent manner and, conversely, that decreasing or increasing the level of PIP2 results in severe F-actin disorganization, revealing the interdependence between these components. Furthermore, we uncovered that PIP2 regulates the sizing of PAR cortical domains. Overall, our work establishes for the first time that a lipid membrane component, PIP2, is a critical modulator of actin organization and cell polarity in C. elegans embryos.\n\nSummary statementPI(4,5)P2 is distributed in dynamic cortical structures and regulates asymmetric division by controlling actin organization and cell polarity in the one-cell C. elegans embryo.

developmental biology