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A role for the CXCR4-CXCL12 axis in the little skate, Leucoraja erinacea.


ABSTRACT: The interaction between C-X-C chemokine receptor type 4 (CXCR4) and its cognate ligand C-X-C motif chemokine ligand 12 (CXCL12) plays a critical role in regulating hematopoietic stem cell activation and subsequent cellular mobilization. Extensive studies of these genes have been conducted in mammals, but much less is known about the expression and function of CXCR4 and CXCL12 in non-mammalian vertebrates. In the present study, we identify simultaneous expression of CXCR4 and CXCL12 orthologs in the epigonal organ (the primary hematopoietic tissue) of the little skate, Leucoraja erinacea. Genetic and phylogenetic analyses were functionally supported by significant mobilization of leukocytes following administration of Plerixafor, a CXCR4 antagonist and clinically important drug. Our results provide evidence that, as in humans, Plerixafor disrupts CXCR4/CXCL12 binding in the little skate, facilitating release of leukocytes into the bloodstream. Our study illustrates the value of the little skate as a model organism, particularly in studies of hematopoiesis and potentially for preclinical research on hematological and vascular disorders.

SUBMITTER: Hersh TA 

PROVIDER: S-EPMC6139610 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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A role for the CXCR4-CXCL12 axis in the little skate, Leucoraja erinacea.

Hersh Taylor A TA   Dimond Alexandria L AL   Ruth Brittany A BA   Lupica Noah V NV   Bruce Jacob C JC   Kelley John M JM   King Benjamin L BL   Lutton Bram V BV  

American journal of physiology. Regulatory, integrative and comparative physiology 20180411 2


The interaction between C-X-C chemokine receptor type 4 (CXCR4) and its cognate ligand C-X-C motif chemokine ligand 12 (CXCL12) plays a critical role in regulating hematopoietic stem cell activation and subsequent cellular mobilization. Extensive studies of these genes have been conducted in mammals, but much less is known about the expression and function of CXCR4 and CXCL12 in non-mammalian vertebrates. In the present study, we identify simultaneous expression of CXCR4 and CXCL12 orthologs in  ...[more]

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