Targeted disruption of cubilin reveals essential developmental roles in the structure and function of endoderm and in somite formation.
| Autor: | Smith BT; Department of Cell Biology and Anatomy Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA. smithbt@musc.edu, Mussell JC, Fleming PA, Barth JL, Spyropoulos DD, Cooley MA, Drake CJ, Argraves WS |
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| Jazyk: | angličtina |
| Zdroj: | BMC developmental biology [BMC Dev Biol] 2006 Jun 20; Vol. 6, pp. 30. Date of Electronic Publication: 2006 Jun 20. |
| DOI: | 10.1186/1471-213X-6-30 |
| Abstrakt: | Background: Cubilin is a peripheral membrane protein that interacts with the integral membrane proteins megalin and amnionless to mediate ligand endocytosis by absorptive epithelia such as the extraembryonic visceral endoderm (VE). Results: Here we report the effects of the genetic deletion of cubilin on mouse embryonic development. Cubilin gene deletion is homozygous embryonic lethal with death occurring between 7.5-13.5 days post coitum (dpc). Cubilin-deficient embryos display developmental retardation and do not advance morphologically beyond the gross appearance of wild-type 8-8.5 dpc embryos. While mesodermal structures such as the allantois and the heart are formed in cubilin mutants, other mesoderm-derived tissues are anomalous or absent. Yolk sac blood islands are formed in cubilin mutants but are unusually large, and the yolk sac blood vessels fail to undergo remodeling. Furthermore, somite formation does not occur in cubilin mutants. Morphological abnormalities of endoderm occur in cubilin mutants and include a stratified epithelium in place of the normally simple columnar VE epithelium and a stratified cuboidal epithelium in place of the normally simple squamous epithelium of the definitive endoderm. Cubilin-deficient VE is also functionally defective, unable to mediate uptake of maternally derived high-density lipoprotein (HDL). Conclusion: In summary, cubilin is required for embryonic development and is essential for the formation of somites, definitive endoderm and VE and for the absorptive function of VE including the process of maternal-embryo transport of HDL. |
| Databáze: | MEDLINE |
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