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Integrin alphaV is necessary for gastrulation movements that regulate vertebrate body asymmetry.

ABSTRACT: Integrin ?V can form heterodimers with several ? subunits to mediate cell-cell and cell-extracellular matrix interactions. During zebrafish gastrulation, ?V is expressed maternally and zygotically. Here, we used a morpholino-mediated ?V knockdown strategy to study ?V function. Although ?V morphants displayed vascular defects, they also exhibited left-right body asymmetry defects affecting multiple visceral organs. This was preceded by mislocalization of dorsal forerunner cells (DFCs) and malformation of the Kupffer's vesicle (KV) laterality organ. These defects were rescued with morpholino-resistant ?V mRNA. Like ?V, integrin ?1b was expressed in DFCs, and ?1b knockdown largely recapitulated the laterality phenotype of ?V morphants. When tracked in real-time, individual DFCs of both morphants showed defects in DFC migration, preventing them from organizing into a KV of normal shape and size. Thus, we propose that ?V?1b mediates cellular interactions that are necessary for DFC clustering and movements necessary for Kupffer's vesicle formation, uncovering an early contribution of integrins to the regulation of vertebrate laterality.

SUBMITTER: Ablooglu AJ

PROVIDER: S-EPMC2947757 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Integrin alphaV is necessary for gastrulation movements that regulate vertebrate body asymmetry.

Ablooglu Ararat J AJ Tkachenko Eugene E Kang Jian J Shattil Sanford J SJ

Development (Cambridge, England) 20100915 20

Integrin αV can form heterodimers with several β subunits to mediate cell-cell and cell-extracellular matrix interactions. During zebrafish gastrulation, αV is expressed maternally and zygotically. Here, we used a morpholino-mediated αV knockdown strategy to study αV function. Although αV morphants displayed vascular defects, they also exhibited left-right body asymmetry defects affecting multiple visceral organs. This was preceded by mislocalization of dorsal forerunner cells (DFCs) and malform ...[more]

PMID: 20843856

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Project description:Metanephrogenesis has been a long-standing model to study cell-matrix interactions. A number of adhesion molecules, including matrix receptors (i.e., integrins), are believed to be involved in such interactions. The integrins contain alpha and beta s ubunits and are present in various tissues in different heterodimeric forms. In this study, one of the members of the integrin superfamily, alphaV, was characterized, and its relevance in murine nephrogenesis was investigated. Mouse embryonic renal cDNA libraries were prepared and screened for alphaV, and multiple clones were isolated and sequenced. The deduced amino acid sequence of the alpha-v cDNA clones and hydropathic analysis revealed that it has a typical signal sequence and extracellular, transmembrane, and cytoplasmic domains, with multiple Ca2+ binding sites. No A(U)nA mRNA instability motifs were present. Conformational analysis revealed no rigid long-range-ordered structure in murine alphaV. The alphaV was expressed in the embryonic kidney at day 13 of the gestation, with a transcript size of approximately 7 kb. Its expression increased progressively during the later gestational stages and in the neonatal period. It was distributed in the epithelial elements of developing nephrons and was absent in the uninduced mesenchyme. In mature metanephroi, the expression was relatively high in the glomeruli and blood vessels, as compared to the tubules. Various heterodimeric associations of alphaV, i.e., with beta1, beta3, beta5, and beta6, were observed in metanephric tissues. Inclusion of alphaV-antisense-oligodeoxynucleotide or -antibody in metanephric culture induced dysmorphogenesis of the kidney with reduced population of the nephrons, disorganization of the ureteric bud branches, and reduction of mRNA and protein expressions of alphaV. The expressions of integrin beta3, beta5, and beta6 were unaltered. These findings suggest that the integrin alphaV is developmentally regulated, has a distinct spatio-temporal expression, and is relevant in the mammalian organogenesis.

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Integrin alphaV is necessary for gastrulation movements that regulate vertebrate body asymmetry.

Publications

Integrin alphaV is necessary for gastrulation movements that regulate vertebrate body asymmetry.

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