Cell Surface Heparan Sulfate Chains Regulate Local Reception of FGF Signaling in the Mouse Embryo

Kayo Shimokawa, Chiharu Kimura-Yoshida, Naoko Nagai, Kazuhiro Mukai, Kazumi Matsubara, Hideto Watanabe, Yoichi Matsuda, Kyoko Mochida, Isao Matsuo

Research output: Contribution to journalArticle

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Abstract

Heparan sulfate (HS) proteoglycans modulate the activity of multiple growth factors on the cell surface and extracellular matrix. However, it remains unclear how the HS chains control the movement and reception of growth factors into targeted receiving cells during mammalian morphogenetic processes. Here, we found that HS-deficient Ext2 null mutant mouse embryos fail to respond to fibroblast growth factor (FGF) signaling.Marker expression analyses revealed that cell surface-tethered HS chains are crucial for local retention of FGF4 and FGF8 ligands in the extraembryonic ectoderm. Fine chimeric studies with single-cell resolution and expression studies with specific inhibitors for HS movement demonstrated that proteolytic cleavage of HS chains can spread FGF signaling to adjacent cells within a short distance. Together, the results show that spatiotemporal expression of cell surface-tethered HS chains regulate the local reception of FGF-signaling activity during mammalian embryogenesis.
Original languageEnglish
Pages (from-to)257-272
Number of pages16
JournalDevelopmental Cell
Volume21
DOIs
Publication statusPublished - 2011
Externally publishedYes

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Heparitin Sulfate
Fibroblast Growth Factors
Embryonic Structures
Intercellular Signaling Peptides and Proteins
Heparan Sulfate Proteoglycans
Ectoderm
Embryonic Development
Extracellular Matrix
Ligands

Cite this

Shimokawa, K., Kimura-Yoshida, C., Nagai, N., Mukai, K., Matsubara, K., Watanabe, H., ... Matsuo, I. (2011). Cell Surface Heparan Sulfate Chains Regulate Local Reception of FGF Signaling in the Mouse Embryo. Developmental Cell, 21, 257-272. https://doi.org/10.1016/j.devcel.2011.06.027
Shimokawa, Kayo ; Kimura-Yoshida, Chiharu ; Nagai, Naoko ; Mukai, Kazuhiro ; Matsubara, Kazumi ; Watanabe, Hideto ; Matsuda, Yoichi ; Mochida, Kyoko ; Matsuo, Isao. / Cell Surface Heparan Sulfate Chains Regulate Local Reception of FGF Signaling in the Mouse Embryo. In: Developmental Cell. 2011 ; Vol. 21. pp. 257-272.
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abstract = "Heparan sulfate (HS) proteoglycans modulate the activity of multiple growth factors on the cell surface and extracellular matrix. However, it remains unclear how the HS chains control the movement and reception of growth factors into targeted receiving cells during mammalian morphogenetic processes. Here, we found that HS-deficient Ext2 null mutant mouse embryos fail to respond to fibroblast growth factor (FGF) signaling.Marker expression analyses revealed that cell surface-tethered HS chains are crucial for local retention of FGF4 and FGF8 ligands in the extraembryonic ectoderm. Fine chimeric studies with single-cell resolution and expression studies with specific inhibitors for HS movement demonstrated that proteolytic cleavage of HS chains can spread FGF signaling to adjacent cells within a short distance. Together, the results show that spatiotemporal expression of cell surface-tethered HS chains regulate the local reception of FGF-signaling activity during mammalian embryogenesis.",
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Shimokawa, K, Kimura-Yoshida, C, Nagai, N, Mukai, K, Matsubara, K, Watanabe, H, Matsuda, Y, Mochida, K & Matsuo, I 2011, 'Cell Surface Heparan Sulfate Chains Regulate Local Reception of FGF Signaling in the Mouse Embryo', Developmental Cell, vol. 21, pp. 257-272. https://doi.org/10.1016/j.devcel.2011.06.027

Cell Surface Heparan Sulfate Chains Regulate Local Reception of FGF Signaling in the Mouse Embryo. / Shimokawa, Kayo; Kimura-Yoshida, Chiharu; Nagai, Naoko; Mukai, Kazuhiro; Matsubara, Kazumi; Watanabe, Hideto; Matsuda, Yoichi; Mochida, Kyoko; Matsuo, Isao.

In: Developmental Cell, Vol. 21, 2011, p. 257-272.

Research output: Contribution to journalArticle

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AU - Shimokawa, Kayo

AU - Kimura-Yoshida, Chiharu

AU - Nagai, Naoko

AU - Mukai, Kazuhiro

AU - Matsubara, Kazumi

AU - Watanabe, Hideto

AU - Matsuda, Yoichi

AU - Mochida, Kyoko

AU - Matsuo, Isao

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AB - Heparan sulfate (HS) proteoglycans modulate the activity of multiple growth factors on the cell surface and extracellular matrix. However, it remains unclear how the HS chains control the movement and reception of growth factors into targeted receiving cells during mammalian morphogenetic processes. Here, we found that HS-deficient Ext2 null mutant mouse embryos fail to respond to fibroblast growth factor (FGF) signaling.Marker expression analyses revealed that cell surface-tethered HS chains are crucial for local retention of FGF4 and FGF8 ligands in the extraembryonic ectoderm. Fine chimeric studies with single-cell resolution and expression studies with specific inhibitors for HS movement demonstrated that proteolytic cleavage of HS chains can spread FGF signaling to adjacent cells within a short distance. Together, the results show that spatiotemporal expression of cell surface-tethered HS chains regulate the local reception of FGF-signaling activity during mammalian embryogenesis.

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