H2020Индивидуална стипендия2016–2018

SUPRACELL_COMMUN_CCT · Supracellular contractility dynamics and cell communication during collective chemotaxis.

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2016-10-01 → 2018-09-30
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Клетъчната комуникация и движението на групи от клетки се изследват чрез пример с невралния гребен при ембрионите. Разбирането на тези процеси помага при изучаването на вродени дефекти и разпространението на някои видове рак.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Supracellular contractility dynamics and cell communication during collective chemotaxis.

Collective chemotaxis, whereby groups of cells move in response to a chemoattractant, is a highly coordinated process underlying development and tumour migration. The Neural Crest (NC) is an invasive mesenchymal cell population that, responding to chemoattractant signals such as Sdf1, migrates throughout the embryo to differentiate into a variety of cell types, in a way that is reminiscent of metastatic migration in some cancer types. NC cells perform chemotaxis much more effectively as a cluster than as single cells, indicating that cell-cell communication improves coordination and directionality. In this project, we addressed the cluster behaviour as a ‘supracellular’ entity, where cell-cell intercellular chemical communication is maintained in order to collectively polarize and migrate. Defective migration of the NC during embryogenesis leads to many human syndromes and birth defects, collectively known as neurocristopathies, and this is why the project is highly relevant for addressing development and diseases. From the results we conclude that ATP, secreted through Connexin hemichannels and sensed via P2Y8 and P2Y11 receptors, controls NC dispersion by regulating cellular levels of the adhesion molecule E-cadherin. Our data support the hypothesis that purinergic and calcium signaling play a main role in regulating the collective behaviour of migrating NC, by coordinating their supracellular organisation. Further investigation is needed to extend these observation to our recently developed Zebrafish model for in-vivo calcium imaging during NC migration, and to assess which other molecular players take part to the pathway regulating E-cadherin expression levels. The results of this project surely will contribute to increasing competitiveness and economical impact of European research worldwide.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Collective chemotaxis (CCT) is a fundamental process for embryonic development and cancer metastasis, where groups of cells collectively migrate in response to a chemoattractive signal. While single cell migration depends on polarised actomyosin mechanotransduction and signalling cascades within the same cell, in CCT these functions are shared between different cells to achieve a coordinated, ‘‘supracellular’’ translocation. The molecular mechanisms underlying coordination and cell-cell communication during CCT have been largely overlooked. I propose to address this issue using the neural crest (NC), a highly invasive mesenchymal cell population that migrates throughout the embryo via CCT. NC migration shows extensive similarities with cancer invasion, making it a useful model for studying metastatic migration. Preliminary experiments show that an actomyosin ring-shaped cable, which surrounds the NC cluster, contributes to maintain a supracellular organisation. Also, during CCT, gap junctions appear to regulate synchronous actomyosin contractions in cells located at the cluster’s rear. Therefore, I will study this contractility dynamics in-vitro and in-vivo using Xenopus and zebrafish. I will manipulate the actomyosin cable to understand its contribution to efficient chemotaxis. Then, I will investigate how gap junctions enable synchronisation between neighbouring cells, by imaging the spread of calcium waves in NC clusters and manipulating other diffusible messengers. This study will give significant insights into the mechanisms regulating CCT, which is crucial for deepening our understanding of morphogenesis and cancer biology.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITY COLLEGE LONDON · LondonКоординаторОбединеното кралство