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LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain barrier formation.

Sohet F, Lin C, Munji RN, Lee SY, Ruderisch N, Soung A, Arnold TD, Derugin N, Vexler ZS, Yen FT, Daneman R - J. Cell Biol. (2015)

Bottom Line: One important BBB property is the formation of a paracellular barrier made by tight junctions (TJs) between CNS endothelial cells (ECs).Here, we show that Lipolysis-stimulated lipoprotein receptor (LSR), a component of paracellular junctions at points in which three cell membranes meet, is greatly enriched in CNS ECs compared with ECs in other nonneural tissues.We demonstrate that LSR is specifically expressed at tricellular junctions and that its expression correlates with the onset of BBB formation during embryogenesis.

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Affiliation: Department of Pharmacology and Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093 Department of Pharmacology and Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093 fsohet@ucsd.edu rdaneman@ucsd.edu.

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LSR expression during embryogenesis. Tissue sections of E11.5 (top), E12.5 (middle), and E13.5 (bottom) mouse embryos were stained with antibodies directed against LSR (red) and CD31 (green). Whole embryos, as well as high-power images of three CNS regions (caudal SC, rostral SC, and forebrain), are shown as well as single-channel images for LSR staining. At E11.5, LSR staining is visualized in CNS blood vessels at the caudal part of the SC only. By E12.5, LSR is expressed throughout the caudal-to-rostral axis of the SC, but not in the forebrain. At E13.5, LSR is expressed in all blood vessels throughout the CNS. Bars: (left) 1.25 mm; (right) 20 µm.
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fig2: LSR expression during embryogenesis. Tissue sections of E11.5 (top), E12.5 (middle), and E13.5 (bottom) mouse embryos were stained with antibodies directed against LSR (red) and CD31 (green). Whole embryos, as well as high-power images of three CNS regions (caudal SC, rostral SC, and forebrain), are shown as well as single-channel images for LSR staining. At E11.5, LSR staining is visualized in CNS blood vessels at the caudal part of the SC only. By E12.5, LSR is expressed throughout the caudal-to-rostral axis of the SC, but not in the forebrain. At E13.5, LSR is expressed in all blood vessels throughout the CNS. Bars: (left) 1.25 mm; (right) 20 µm.

Mentions: We sought to determine the time course of LSR expression during development. Angiogenesis in the mouse CNS initiates at E9, and proceeds in a caudal-to-rostral direction. We examined LSR expression in the CNS of embryos from E10 onwards (Fig. 2). At E11.5, LSR is expressed throughout the cellular membrane of CNS ECs only at the caudal part of the SC. By E12.5, LSR expression is still diffuse throughout the EC membrane, but is expressed in vessels throughout the caudal–rostral axis of the SC and is absent from forebrain ECs. At E13.5, LSR is expressed in all blood vessels throughout the CNS including the brain, but this expression still appears to be diffuse throughout the EC membrane. Thus, LSR expression follows angiogenesis in a caudal-to-rostral direction from E11.5 to E13.5. At postnatal day 3 (P3), LSR is localized mainly at the bicellular/tricellular TJs, whereas at P12 the protein is further accumulated at the tricellular TJ and by P21 the protein is largely enriched at the tricellular junction as it is in the adult (Fig. S1 C and Fig. 1 B). Our results indicate that CNS EC expression of LSR follows slightly behind CNS angiogenesis, and as development proceeds more LSR is concentrated at the tricellular TJ of CNS blood vessels.


LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain barrier formation.

Sohet F, Lin C, Munji RN, Lee SY, Ruderisch N, Soung A, Arnold TD, Derugin N, Vexler ZS, Yen FT, Daneman R - J. Cell Biol. (2015)

LSR expression during embryogenesis. Tissue sections of E11.5 (top), E12.5 (middle), and E13.5 (bottom) mouse embryos were stained with antibodies directed against LSR (red) and CD31 (green). Whole embryos, as well as high-power images of three CNS regions (caudal SC, rostral SC, and forebrain), are shown as well as single-channel images for LSR staining. At E11.5, LSR staining is visualized in CNS blood vessels at the caudal part of the SC only. By E12.5, LSR is expressed throughout the caudal-to-rostral axis of the SC, but not in the forebrain. At E13.5, LSR is expressed in all blood vessels throughout the CNS. Bars: (left) 1.25 mm; (right) 20 µm.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4362448&req=5

fig2: LSR expression during embryogenesis. Tissue sections of E11.5 (top), E12.5 (middle), and E13.5 (bottom) mouse embryos were stained with antibodies directed against LSR (red) and CD31 (green). Whole embryos, as well as high-power images of three CNS regions (caudal SC, rostral SC, and forebrain), are shown as well as single-channel images for LSR staining. At E11.5, LSR staining is visualized in CNS blood vessels at the caudal part of the SC only. By E12.5, LSR is expressed throughout the caudal-to-rostral axis of the SC, but not in the forebrain. At E13.5, LSR is expressed in all blood vessels throughout the CNS. Bars: (left) 1.25 mm; (right) 20 µm.
Mentions: We sought to determine the time course of LSR expression during development. Angiogenesis in the mouse CNS initiates at E9, and proceeds in a caudal-to-rostral direction. We examined LSR expression in the CNS of embryos from E10 onwards (Fig. 2). At E11.5, LSR is expressed throughout the cellular membrane of CNS ECs only at the caudal part of the SC. By E12.5, LSR expression is still diffuse throughout the EC membrane, but is expressed in vessels throughout the caudal–rostral axis of the SC and is absent from forebrain ECs. At E13.5, LSR is expressed in all blood vessels throughout the CNS including the brain, but this expression still appears to be diffuse throughout the EC membrane. Thus, LSR expression follows angiogenesis in a caudal-to-rostral direction from E11.5 to E13.5. At postnatal day 3 (P3), LSR is localized mainly at the bicellular/tricellular TJs, whereas at P12 the protein is further accumulated at the tricellular TJ and by P21 the protein is largely enriched at the tricellular junction as it is in the adult (Fig. S1 C and Fig. 1 B). Our results indicate that CNS EC expression of LSR follows slightly behind CNS angiogenesis, and as development proceeds more LSR is concentrated at the tricellular TJ of CNS blood vessels.

Bottom Line: One important BBB property is the formation of a paracellular barrier made by tight junctions (TJs) between CNS endothelial cells (ECs).Here, we show that Lipolysis-stimulated lipoprotein receptor (LSR), a component of paracellular junctions at points in which three cell membranes meet, is greatly enriched in CNS ECs compared with ECs in other nonneural tissues.We demonstrate that LSR is specifically expressed at tricellular junctions and that its expression correlates with the onset of BBB formation during embryogenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology and Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093 Department of Pharmacology and Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093 fsohet@ucsd.edu rdaneman@ucsd.edu.

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Related in: MedlinePlus