The intestinal brush border is made of an array of microvilli that increases the membrane surface area for nutrient processing, absorption, and host defense. 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 brush border markers. 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 toolbox 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.
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, structural components 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 when 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 the brush border integrity.
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.
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