Dataset Information

Loss of Cubilin, the intrinsic factor-vitamin B12 receptor, impairs visceral endoderm endocytosis and endodermal patterning in the mouse.

ABSTRACT: The visceral endoderm is a polarized epithelial monolayer necessary for early embryonic development in rodents. A key feature of this epithelium is an active endocytosis and degradation of maternal nutrients, in addition to being the source of various signaling molecules or inhibitors required for the differentiation and patterning of adjacent embryonic tissues. Endocytosis across the visceral endoderm epithelium involves specific cell surface receptors and an extensive sub-membrane vesicular system with numerous apical vacuoles/lysosomes. We previously reported that Cubilin, the endocytic receptor for intrinsic factor-vitamin B12, albumin and apolipoproteinA-I/HDL allows maternal nutrient uptake by the visceral endoderm. In the present study, we show that the germline ablation of Cubilin impairs endodermal and mesodermal patterning, and results in developmental arrest at gastrulation. Notably, visceral endoderm dispersal is impeded in Cubilin null embryos. We further confirm the essential role of Cubilin in nutrient internalization by the early visceral endoderm and highlight its involvement in the formation of apical vacuoles. Our results reveal essential roles for Cubilin in early embryonic development, and suggest that in addition to its nutritive function, Cubilin sustains signaling pathways involved in embryonic differentiation and patterning.

SUBMITTER: Perea-Gomez A

PROVIDER: S-EPMC6629654 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Loss of Cubilin, the intrinsic factor-vitamin B12 receptor, impairs visceral endoderm endocytosis and endodermal patterning in the mouse.

Perea-Gomez Aitana A Cases Olivier O Lelièvre Vincent V Pulina Maria V MV Collignon Jérôme J Hadjantonakis Anna-Katerina AK Kozyraki Renata R

Scientific reports 20190715 1

The visceral endoderm is a polarized epithelial monolayer necessary for early embryonic development in rodents. A key feature of this epithelium is an active endocytosis and degradation of maternal nutrients, in addition to being the source of various signaling molecules or inhibitors required for the differentiation and patterning of adjacent embryonic tissues. Endocytosis across the visceral endoderm epithelium involves specific cell surface receptors and an extensive sub-membrane vesicular sy ...[more]

PMID: 31308417

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Project description:The visceral endoderm (VE) is a simple epithelium that forms the outer layer of the egg-cylinder stage mouse embryo. The anterior visceral endoderm (AVE), a specialised subset of VE cells, is responsible for specifying anterior pattern. AVE cells show a stereotypic migratory behaviour within the VE, which is responsible for correctly orientating the anterior-posterior axis. The epithelial integrity of the VE is maintained during the course of AVE migration, which takes place by intercalation of AVE and other VE cells. Though a continuous epithelial sheet, the VE is characterised by two regions of dramatically different behaviour, one showing robust cell movement and intercalation (in which the AVE migrates) and one that is static, with relatively little cell movement and mixing. Little is known about the cellular rearrangements that accommodate and influence the sustained directional movement of subsets of cells (such as the AVE) within epithelia like the VE. This study uses an interdisciplinary approach to further our understanding of cell movement in epithelia. Using both wild-type embryos as well as mutants in which AVE migration is abnormal or arrested, we show that AVE migration is specifically linked to changes in cell packing in the VE and an increase in multi-cellular rosette arrangements (five or more cells meeting at a point). To probe the role of rosettes during AVE migration, we develop a mathematical model of cell movement in the VE. To do this, we use a vertex-based model, implemented on an ellipsoidal surface to represent a realistic geometry for the mouse egg-cylinder. The potential for rosette formation is included, along with various junctional rearrangements. Simulations suggest that while rosettes are not essential for AVE migration, they are crucial for the orderliness of this migration observed in embryos. Our simulations are similar to results from transgenic embryos in which Planar Cell Polarity (PCP) signalling is disrupted. Such embryos have significantly reduced rosette numbers, altered epithelial packing, and show abnormalities in AVE migration. Our results show that the formation of multi-cellular rosettes in the mouse VE is dependent on normal PCP signalling. Taken together, our model and experimental observations suggest that rosettes in the VE epithelium do not form passively in response to AVE migration. Instead, they are a PCP-dependent arrangement of cells that acts to buffer the disequilibrium in cell packing generated in the VE by AVE migration, enabling AVE cells to migrate in an orderly manner.

Dataset Information

Loss of Cubilin, the intrinsic factor-vitamin B12 receptor, impairs visceral endoderm endocytosis and endodermal patterning in the mouse.

Publications

Loss of Cubilin, the intrinsic factor-vitamin B12 receptor, impairs visceral endoderm endocytosis and endodermal patterning in the mouse.

Similar Datasets

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