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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Nyckelord

epiblast

epithelial polarity

stem cells

mouse development

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