Biology subjects

Pacquelet, A.

Publications and source records attributed to Pacquelet, A..

4 recordsLinked to original sources

bioRxiv2024

The proliferation and differentiation programs are only partially coupled during C. elegans intestine development

Cell proliferation and differentiation are essential processes underlying multicellular organism development. Cell proliferation arrest usually precedes terminal differentiation, suggesting that these two processes may be coordinated. Here we took advantage of the very stereotyped development of the C. elegans intestine to address whether the control of the proliferation and differentiation programs are systematically coupled. We show that delaying cell cycle arrest does not affect most aspects of intestinal differentiation but leads to a specific delay in the accumulation of late microvilli components. Reciprocally, we find that the differentiation factors ELT-2 and ELT-7 control cell cycle arrest specifically in posterior enterocytes. The occurrence of supernumerary divisions in the absence of ELT-2 and ELT-7 is associated with changes in the expression pattern of the cell cycle regulators cyclin B1 and CKI-1 and depends on the presence of the posterior Hox protein PHP-3. Our work thus demonstrates the existence of reciprocal interactions between cell proliferation and cell differentiation. It nevertheless also shows that these two processes are only partially coupled, suggesting the existence of additional mechanisms ensuring their temporal control.

developmental biology↗

bioRxiv2022

PAR-4/LKB1 regulates intestinal cell number by restricting endoderm specification to the E lineage

The master kinase PAR-4/LKB1 appears as a major regulator of intestinal physiology. It is in particular mutated in the Peutz-Jeghers syndrome, an inherited disorder in which patients develop benign intestine polyps. Moreover, ectopic activation of PAR-4/LKB1 is sufficient to induce the polarized accumulation of apical and basolateral surface proteins and the formation of apical microvilli-like structures in intestinal epithelial cancer cell lines. In C. elegans, PAR-4 was shown to be required for the differentiation of intestinal cells. Here, we further examine the role of PAR-4 during intestinal development. We find that it is not required for the establishment of enterocyte polarity and plays only a minor role in brush border formation. By contrast, par-4 mutants display severe deformations of the intestinal lumen as well as supernumerary intestinal cells, thereby revealing a novel function of PAR-4 in preventing intestinal hyperplasia. Importantly, we find that the ability of PAR-4 to control intestinal cell number does not involve the regulation of cell proliferation but is rather due to its ability to restrict the expression of intestinal cell fate factors to the E blastomere lineage. We therefore propose that PAR-4 is required to regulate C. elegans intestine specification.

developmental biology↗

bioRxiv2021

High resolution dynamic mapping of the C. elegans intestinal brush border

The intestinal brush border is made of an array of microvilli that increases the membrane surface area for nutrient processing, absorption, and host defence. Studies on mammalian cultured epithelial cells uncovered some of the molecular players and physical constrains required to establish this apical specialized membrane. However, the building and maintenance of a brush border in vivo has not been investigated in detail yet. Here, we combined super-resolution imaging, transmission electron microscopy and genome editing in the developing nematode C. elegans to build a high-resolution and dynamic localization map of known and new markers of the brush border. Notably, we show that microvilli components are dynamically enriched at the apical membrane during microvilli outgrowth and maturation but become highly stable once microvilli are built. This new mapping tool will be instrumental to understand the molecular processes of microvilli growth and maintenance in vivo as well as the effect of genetic perturbations, notably in the context of disorders affecting brush border integrity.

developmental biology↗

bioRxiv2019

Simultaneous regulation of cytokinetic furrow and nucleus positions by cortical tension contributes to proper DNA segregation during late mitosis

Coordinating mitotic spindle and cytokinetic furrow positioning is essential to ensure proper DNA segregation. Here we present a novel mechanism, which corrects DNA segregation defects due to cytokinetic furrow mispositioning. We show that DNA segregation defects following the abnormal displacement of the cytokinetic furrow towards the anterior side of C. elegans one-cell embryos are unexpectedly corrected at the end of cytokinesis. This correction relies on the concomitant displacement of the furrow and of the anterior nucleus towards the posterior and anterior poles, respectively. It also coincides with cortical blebbing and an anteriorly directed flow of cytoplasmic particles. While microtubules contribute to nuclear displacement, relaxation of an excessive tension at the anterior cortex plays a central role in the correction process and simultaneously regulates cytoplasmic flow as well as nuclear and furrow displacements. This work thus reveals the existence of a so far uncharacterized correction mechanism, which is critical to correct DNA segregation defects due to cytokinetic furrow mispositioning.

cell biology↗