LymphedemaV1, Main, Exploration, bibRecord, 006128

Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85α, p55α, and p50α

Identifieur interne : 006128 ( Main/Exploration ); précédent : 006127; suivant : 006129

Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85α, p55α, and p50α

Auteurs : Carla Mouta-Bellum ; Aleksander Kirov ; Laura Miceli-Libby ; Maria L. Mancini ; Tatiana V. Petrova ; Lucy Liaw ; Igor Prudovsky ; Philip E. Thorpe [États-Unis] ; Naoyuki Miura ; Lewis C. Cantley [États-Unis] ; Kari Alitalo [Finlande] ; David A. Fruman [États-Unis] ; Calvin P. H. Vary

Source :

Developmental dynamics : an official publication of the American Association of Anatomists [ 1058-8388 ] ; 2009.

RBID : PMC:2826787

Abstract

The phosphoinositide 3-kinase (PI3K) family has multiple vascular functions, but the specific regulatory isoform supporting lymphangiogenesis remains unidentified. Here we report that deletion of the Pik3r1 gene, encoding the regulatory subunits p85α, p55α, and p50α impairs lymphatic sprouting and maturation, and causes abnormal lymphatic morphology, without major impact on blood vessels. Pik3r1 deletion had the most severe consequences among gut and diaphragm lymphatics, which share the retroperitoneal anlage, initially suggesting that the Pik3r1 role in this vasculature is anlage-dependent. However, whereas lymphatic sprouting toward the diaphragm was arrested, lymphatics invaded the gut, where remodeling and valve formation were impaired. Thus, cell-origin fails to explain the phenotype. Only the gut showed lymphangiectasia, lymphatic up-regulation of the TGFβ co-receptor endoglin, and reduced levels of mature VEGF-C protein. Our data suggest that Pik3r1 isoforms are required for distinct steps of embryonic lymphangiogenesis in different organ microenvironments, whereas they are largely dispensable for hemangiogenesis.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826787

DOI: 10.1002/dvdy.22078
PubMed: 19705443
PubMed Central: 2826787

Affiliations:

Le document en format XML

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<front><div type="abstract" xml:lang="en"><p id="P1">The phosphoinositide 3-kinase (PI3K) family has multiple vascular functions, but the specific regulatory isoform supporting lymphangiogenesis remains unidentified. Here we report that deletion of the <italic>Pik3r1</italic>
 gene, encoding the regulatory subunits p85α, p55α, and p50α impairs lymphatic sprouting and maturation, and causes abnormal lymphatic morphology, without major impact on blood vessels. <italic>Pik3r1</italic>
 deletion had the most severe consequences among gut and diaphragm lymphatics, which share the retroperitoneal anlage, initially suggesting that the <italic>Pik3r1</italic>
 role in this vasculature is anlage-dependent. However, whereas lymphatic sprouting toward the diaphragm was arrested, lymphatics invaded the gut, where remodeling and valve formation were impaired. Thus, cell-origin fails to explain the phenotype. Only the gut showed lymphangiectasia, lymphatic up-regulation of the TGFβ co-receptor endoglin, and reduced levels of mature VEGF-C protein. Our data suggest that <italic>Pik3r1</italic>
 isoforms are required for distinct steps of embryonic lymphangiogenesis in different organ microenvironments, whereas they are largely dispensable for hemangiogenesis.</p>
</div>
</front>
</TEI>
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<tree><noCountry><name sortKey="Kirov, Aleksander" sort="Kirov, Aleksander" uniqKey="Kirov A" first="Aleksander" last="Kirov">Aleksander Kirov</name>
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<name sortKey="Mancini, Maria L" sort="Mancini, Maria L" uniqKey="Mancini M" first="Maria L." last="Mancini">Maria L. Mancini</name>
<name sortKey="Miceli Libby, Laura" sort="Miceli Libby, Laura" uniqKey="Miceli Libby L" first="Laura" last="Miceli-Libby">Laura Miceli-Libby</name>
<name sortKey="Miura, Naoyuki" sort="Miura, Naoyuki" uniqKey="Miura N" first="Naoyuki" last="Miura">Naoyuki Miura</name>
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<name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name>
<name sortKey="Prudovsky, Igor" sort="Prudovsky, Igor" uniqKey="Prudovsky I" first="Igor" last="Prudovsky">Igor Prudovsky</name>
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<name sortKey="Cantley, Lewis C" sort="Cantley, Lewis C" uniqKey="Cantley L" first="Lewis C." last="Cantley">Lewis C. Cantley</name>
<name sortKey="Fruman, David A" sort="Fruman, David A" uniqKey="Fruman D" first="David A." last="Fruman">David A. Fruman</name>
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<country name="Finlande"><region name="Uusimaa"><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name>
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Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85α, p55α, and p50α

Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85α, p55α, and p50α

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Abstract

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