The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport
Open accessAbstract
The small intestine is a dynamic and complex organ that is characterized by constant epithelium turnover and crosstalk among various cell types and the microbiota. Lymphatic capillaries of the small intestine, called lacteals, play key roles in dietary fat absorption and the gut immune response; however, little is known about the molecular regulation of lacteal function. Here, we performed a high-resolution analysis of the small intestinal stroma and determined that lacteals reside in a permanent regenerative, proliferative state that is distinct from embryonic lymphangiogenesis or quiescent lymphatic vessels observed in other tissues. We further demonstrated that this continuous regeneration process is mediated by Notch signaling and that the expression of the Notch ligand delta-like 4 (DLL4) in lacteals requires activation of VEGFR3 and VEGFR2. Moreover, genetic inactivation of Dll4 in lymphatic endothelial cells led to lacteal regression and impaired dietary fat uptake. We propose that such a slow lymphatic regeneration mode is necessary to match a unique need of intestinal lymphatic vessels for both continuous maintenance, due to the constant exposure to dietary fat and mechanical strain, and efficient uptake of fat and immune cells. Our work reveals how lymphatic vessel responses are shaped by tissue specialization and uncover a role for continuous DLL4 signaling in the function of adult lymphatic vasculature.
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Cites
Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis
Bevins, C. L., & Salzman, N. H. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2546 · Cited by 1,238
Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut
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Identification and functional analysis of endothelial tip cell–enriched genes
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Self-citationIntegrin-α9 Is Required for Fibronectin Matrix Assembly during Lymphatic Valve Morphogenesis
Bazigou, E., Xie, S., Chen, C., Weston, A., Miura, N., Sorokin, L., Adams, R., Muro, A. F., Sheppard, D., & Makinen, T. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.017 · Cited by 347
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The Notch1-Dll4 signaling pathway regulates mouse postnatal lymphatic development
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Tbx1 regulates Vegfr3 and is required for lymphatic vessel development
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Cited by
Vascular heterogeneity and specialization in development and disease
Potente, M., & Mäkinen, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.36 · Cited by 653
Distinct Mesenchymal Cell Populations Generate the Essential Intestinal BMP Signaling Gradient
McCarthy, N., Manieri, E., Storm, E. E., Saadatpour, A., Luoma, A. M., Kapoor, V. N., Madha, S., Gaynor, L. T., Cox, C., Keerthivasan, S., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.01.008 · Cited by 361
Lymphatic Vessel Network Structure and Physiology
Breslin, J. W., Yang, Y., Scallan, J. P., Sweat, R. S., Adderley, S. P., & Murfee, W. L. (2018) · Comprehensive Physiology · doi:10.1002/cphy.c180015 · Cited by 341
Organ-specific lymphatic vasculature: From development to pathophysiology
Petrova, T. V., & Koh, G. Y. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20171868 · Cited by 304
Self-citationLacteal junction zippering protects against diet-induced obesity
Zhang, F., Zarkada, G., Han, J., Li, J., Dubrac, A., Ola, R., Genet, G., Boyé, K., Michon, P., Künzel, S. E., et al. (2018) · Science · doi:10.1126/science.aap9331 · Cited by 237
Metadata
- Authors
- Bernier-Latmani, J., Cisarovsky, C., Demir, C. S., Bruand, M., Jaquet, M., Davanture, S., Ragusa, S., Siegert, S., Dormond, O., Benedito, R., Radtke, F., Luther, S. A., & Petrova, T. V.
- Venue
- Journal of Clinical Investigation
- Published
- 2015-11-03
- Volume
- 125
- Issue
- 12
- Pages
- 4572-4586
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W1923042616
- Cited by
- 185
- References
- 9
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Bernier-Latmani, J., Cisarovsky, C., Demir, C. S., Bruand, M., Jaquet, M., Davanture, S., Ragusa, S., Siegert, S., Dormond, O., Benedito, R., Radtke, F., Luther, S. A., & Petrova, T. V. (2015). DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport. Journal of Clinical Investigation. https://doi.org/10.1172/jci82045
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