Système endocrinien | EPFL Graph Search

vignette|Principales glandes du système hormonal ; 1 et 2 Épiphyse, hypophyse et hypothalamus 3 - Thyroïde 4 - Thymus 5 - Surrénales 6 - Pancréas endocrine 7 - Ovaires 8 - Testicules Le système endocrinien est composé par l'ensemble des organes qui ont la capacité de relâcher des hormones dans le sang. Les cellules endocriniennes peuvent se situer dans un organe spécialisé dans la sécrétion d'hormones ; une glande endocrine, ou bien au sein d'un organe en amas de cellules endocrines ou en cellules isolées (système endocrinien diffus). L’étymologie du mot endocrine provient du grec ἔνδον, endos, « à l'intérieur » et κρίνω, krino « sécréter ».'' Généralités Le système endocrinien comprend les organes et les glandes qui élaborent des hormones. Ces dernières sont des substances chimiques de signalisation qui sont véhiculées et distribuées par la circulation sanguine dans le corps. Les hormones ont une fonction de contrôle des process

Neurogenin3 Initiates Stepwise Delamination of Differentiating Endocrine Cells During Pancreas Development

Mathieu Gouzi, Anne Grapin-Botton, Keiichi Katsumoto, Yung Hae Kim

During development, pancreatic endocrine cells are specified within the pancreatic epithelium. They subsequently delaminate out of the epithelium and cluster in the mesenchyme to form the islets of Langerhans. Neurogenin3 (Ngn3) is a transcription factor required for the differentiation of all endocrine cells and we investigated its role in their delamination. We observed in the mouse pancreas that most Ngn3-positive cells have lost contact with the lumen of the epithelium, showing that the delamination from the progenitor layer is initiated in endocrine progenitors. Subsequently, in both mouse and chick newly born endocrine cells at the periphery of the epithelium strongly decrease E-cadherin, break-down the basal lamina and cluster into islets of Langerhans. Repression of E-cadherin is sufficient to promote delamination from the epithelium. We further demonstrate that Ngn3 indirectly controls Snail2 protein expression post-transcriptionally to repress E-cadherin. In the chick embryo, Ngn3 independently controls epithelium delamination and differentiation programs. Developmental Dynamics 240:589-604, 2011. (C) 2011 Wiley-Liss, Inc.

2011

Role of Neurogenin3 in migration of pancreatic endocrine cells during development

Mathieu Gouzi

The pancreas is one of the major organs of the digestive tract. Its endocrine function, mainly regulating glucose blood level, is achieved by endocrine cells. These cells are organized in clusters, the so-called islets of Langerhans. During development, these cells are specified within the pancreatic epithelium, and will subsequently delaminate and migrate out of the epithelium in order to form the islets. Neurogenin3 (Ngn3) is a bHLH transcription factor that is responsible for the differentiation of all endocrine cell types, but whether or not it has a role in their migration is still an open question. By using the chicken embryo model organism, we found that the differentiation and migration programs are two different processes that are induced by Ngn3 and that can be uncoupled. Therefore, we tried to unravel the mechanisms by which Ngn3 can induce endocrine cell migration. We found that, in both chick and mouse models, over-expression of Ngn3 induces a loss of apico-basal polarity, a breakdown of basal lamina, and more importantly, a loss of the epithelial marker E-cadherin (E-cad). It seems that this is not a direct effect mediated by direct binding to E-boxes in the E-cad promoter. Therefore, we are currently trying to find targets of Ngn3 that could mediate repression of E-cad, focusing on the zinc-finger transcription factors Snail1 and Snail2. Moreover, we also used a pancreatic explant culture method, developed in the laboratory of Pr. Jonathan Slack, which allows us to do time-lapse imaging and describe precisely the migration of endocrine cells in a system similar to in vivo conditions. Taking advantage of our Pdx1::Ngn3ERTM transgenic line, we followed Ngn3 misexpressing cells to understand in a more physiological manner how they migrate in the developing pancreas. We found that endocrine cell migrate at an average speed of 11.35 µm/h and migrate through an average length of 132.30 µm in 12 hours. We also found that endocrine cells migrate in the three compartments we defined: in the mesenchyme, inside the epithelium and at the edge of the epithelium. Their average velocity significantly changes depending on the compartment cells are migrating in. We found that the fastest cells are the ones migrating at the edge of the epithelium. RNA profiling comparing Ngn3 knockouts rescued or not by the Pdx1::Ngn3ERTM transgene was also used to identify the genes that function in endocrine cell migration downstream of Ngn3. We identified new Ngn3 target genes, some of which are implicated in migration such as the Doublecortin family.

EPFL2010

Cell Cycle-Dependent Differentiation Dynamics Balances Growth and Endocrine Differentiation in the Pancreas

Anne Grapin-Botton, Yung Hae Kim, Laurence Anne E Lemaire

Organogenesis relies on the spatiotemporal balancing of differentiation and proliferation driven by an expanding pool of progenitor cells. In the mouse pancreas, lineage tracing at the population level has shown that the expanding pancreas progenitors can initially give rise to all endocrine, ductal, and acinar cells but become bipotent by embryonic day 13.5, giving rise to endocrine cells and ductal cells. However, the dynamics of individual progenitors balancing self-renewal and lineage-specific differentiation has never been described. Using three-dimensional live imaging and in vivo clonal analysis, we reveal the contribution of individual cells to the global behaviour and demonstrate three modes of progenitor divisions: symmetric renewing, symmetric endocrinogenic, and asymmetric generating a progenitor and an endocrine progenitor. Quantitative analysis shows that the endocrine differentiation process is consistent with a simple model of cell cycle-dependent stochastic priming of progenitors to endocrine fate. The findings provide insights to define control parameters to optimize the generation of beta-cells in vitro.

Public Library Science2015

Role of Neurogenin3 in migration of pancreatic endocrine cells during development

Mathieu Gouzi

EPFL2010