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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Susanne Schéele
  • Mats Falk
  • Ahnders Franzén
  • Fredrik Ellin
  • Maria Ferletta
  • Peter Lonai
  • Björn Andersson
  • Rupert Timpl
  • Erik Forsberg
  • Peter Ekblom
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
  • Medicinska grundvetenskaper

Nyckelord

Originalspråkengelska
Sidor (från-till)1502-1506
TidskriftProceedings of the National Academy of Sciences
Volym102
Utgivningsnummer5
StatusPublished - 2005
PublikationskategoriForskning
Peer review utfördJa