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

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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; Falk, Mats; Franzén, Ahnders; Ellin, Fredrik; Ferletta, Maria; Lonai, Peter; Andersson, Björn; Timpl, Rupert; Forsberg, Erik; Ekblom, Peter.

I: Proceedings of the National Academy of Sciences, Vol. 102, Nr. 5, 2005, s. 1502-1506.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Schéele, S, Falk, M, Franzén, A, Ellin, F, Ferletta, M, Lonai, P, Andersson, B, Timpl, R, Forsberg, E & Ekblom, P 2005, 'Laminin {alpha}1 globular domains 4-5 induce fetal development but are not vital for embryonic basement membrane assembly.', Proceedings of the National Academy of Sciences, vol. 102, nr. 5, s. 1502-1506. https://doi.org/10.1073/pnas.0405095102

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Author

Schéele, Susanne ; Falk, Mats ; Franzén, Ahnders ; Ellin, Fredrik ; Ferletta, Maria ; Lonai, Peter ; Andersson, Björn ; Timpl, Rupert ; Forsberg, Erik ; Ekblom, Peter. / Laminin {alpha}1 globular domains 4-5 induce fetal development but are not vital for embryonic basement membrane assembly. I: Proceedings of the National Academy of Sciences. 2005 ; Vol. 102, Nr. 5. s. 1502-1506.

RIS

TY - JOUR

T1 - Laminin {alpha}1 globular domains 4-5 induce fetal development but are not vital for embryonic basement membrane assembly.

AU - Schéele, Susanne

AU - Falk, Mats

AU - Franzén, Ahnders

AU - Ellin, Fredrik

AU - Ferletta, Maria

AU - Lonai, Peter

AU - Andersson, Björn

AU - Timpl, Rupert

AU - Forsberg, Erik

AU - Ekblom, Peter

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - epiblast

KW - epithelial polarity

KW - stem cells

KW - mouse development

U2 - 10.1073/pnas.0405095102

DO - 10.1073/pnas.0405095102

M3 - Article

VL - 102

SP - 1502

EP - 1506

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 5

ER -