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Laminin {alpha}1 globular domains 4-5 induce fetal development but are not vital for embryonic basement membrane assembly.

Schéele, Susanne LU ; Falk, Mats; Franzén, Ahnders LU ; Ellin, Fredrik; Ferletta, Maria; Lonai, Peter; Andersson, Björn; Timpl, Rupert; Forsberg, Erik and Ekblom, Peter LU (2005) In Proceedings of the National Academy of Sciences 102(5). p.1502-1506
Abstract
basement membrane (BM) assembly, which is required for pregastrulation development. Individual domains may have other functions, not necessarily structural. The cell binding C terminus of Lm {alpha}1 chain contains five Lm globular (LG) domains. In vitro, {alpha}1LG1–3 domains bind integrins, and {alpha}1LG4 binds dystroglycan, heparin, and sulfatides. A prevailing hypothesis is that {alpha}1LG4 is crucial as a structural domain for BM assembly, whereas integrin-binding sites conduct signaling. The in vivo role of {alpha}1LG4–5 (also called E3) has not been studied. Mice lacking {alpha}1LG4–5 were therefore made. Null embryos implanted, but presumptive epiblast cells failed to polarize and did not survive past day 6.5. BM components... (More)
basement membrane (BM) assembly, which is required for pregastrulation development. Individual domains may have other functions, not necessarily structural. The cell binding C terminus of Lm {alpha}1 chain contains five Lm globular (LG) domains. In vitro, {alpha}1LG1–3 domains bind integrins, and {alpha}1LG4 binds dystroglycan, heparin, and sulfatides. A prevailing hypothesis is that {alpha}1LG4 is crucial as a structural domain for BM assembly, whereas integrin-binding sites conduct signaling. The in vivo role of {alpha}1LG4–5 (also called E3) has not been studied. Mice lacking {alpha}1LG4–5 were therefore made. Null embryos implanted, but presumptive epiblast cells failed to polarize and did not survive past day 6.5. BM components including truncated Lm {alpha}1 were detected in Reichert's membrane. Surprisingly, embryonic BM assembly between visceral endoderm and stem cells was normal in null embryos and in embryoid bodies of {alpha}1LG4–5-null embryonic stem cells. Yet, stem cells could not develop into polarized epiblast cells. Thus, {alpha}1LG4–5 provides vital signals for the conversion of stem cells to polarized epithelium. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
epiblast, epithelial polarity, stem cells, mouse development
in
Proceedings of the National Academy of Sciences
volume
102
issue
5
pages
1502 - 1506
publisher
National Acad Sciences
external identifiers
  • wos:000226877300046
  • scopus:13444265889
ISSN
1091-6490
DOI
10.1073/pnas.0405095102
language
English
LU publication?
yes
id
a01ef637-b48b-439e-bcff-18019ba716e4 (old id 132950)
date added to LUP
2007-07-19 12:32:56
date last changed
2017-10-22 03:56:59
@article{a01ef637-b48b-439e-bcff-18019ba716e4,
  abstract     = {basement membrane (BM) assembly, which is required for pregastrulation development. Individual domains may have other functions, not necessarily structural. The cell binding C terminus of Lm {alpha}1 chain contains five Lm globular (LG) domains. In vitro, {alpha}1LG1–3 domains bind integrins, and {alpha}1LG4 binds dystroglycan, heparin, and sulfatides. A prevailing hypothesis is that {alpha}1LG4 is crucial as a structural domain for BM assembly, whereas integrin-binding sites conduct signaling. The in vivo role of {alpha}1LG4–5 (also called E3) has not been studied. Mice lacking {alpha}1LG4–5 were therefore made. Null embryos implanted, but presumptive epiblast cells failed to polarize and did not survive past day 6.5. BM components including truncated Lm {alpha}1 were detected in Reichert's membrane. Surprisingly, embryonic BM assembly between visceral endoderm and stem cells was normal in null embryos and in embryoid bodies of {alpha}1LG4–5-null embryonic stem cells. Yet, stem cells could not develop into polarized epiblast cells. Thus, {alpha}1LG4–5 provides vital signals for the conversion of stem cells to polarized epithelium.},
  author       = {Schéele, Susanne and Falk, Mats and Franzén, Ahnders and Ellin, Fredrik and Ferletta, Maria and Lonai, Peter and Andersson, Björn and Timpl, Rupert and Forsberg, Erik and Ekblom, Peter},
  issn         = {1091-6490},
  keyword      = {epiblast,epithelial polarity,stem cells,mouse development},
  language     = {eng},
  number       = {5},
  pages        = {1502--1506},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Laminin {alpha}1 globular domains 4-5 induce fetal development but are not vital for embryonic basement membrane assembly.},
  url          = {http://dx.doi.org/10.1073/pnas.0405095102},
  volume       = {102},
  year         = {2005},
}