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The Roles of Chemokines During Hematopoiesis of the Amphibian Xenopus Laevis Open Access

Across all vertebrates, hematopoiesis (blood cell development) occurs in designated sites. In the Xenopus laevis frog, the main site for hematopoiesis is thought to be the liver periphery (LP). However, macrophage precursors are not found in the LP and instead they reside in the bone marrow. Because of this unique strategy of dividing hematopoiesis across multiple tissues, X. laevis is a useful model to study blood cell development, enabling us to better understand the evolution of hematopoiesis across vertebrates. We hypothesized that macrophage precursor cells are produced in the LP and migrate to the bone marrow in response to chemokines produced by the bone marrow stroma (BMS). To test this hypothesis, adult X. laevis frogs were injected with erythropoietin (EPO), a growth factor for red blood cells, or colony stimulating factor-1 (CSF-1), a growth factor for macrophages. Following these stimulations, frog LP and BMS cells were isolated and processed for gene expression analyses. Transcript levels of a select panel of chemokines (cxcl12, ccl19, cxcl10, ccl3, cxcl16) were assessed in BMS and LP. We observed that in control animals cxcl12 exhibited significantly greater gene expression in BMS compared to LP. Interestingly, animals injected with CSF-1 displayed significantly greater transcript levels of ccl19 and cxcl10 in both BMS and the LP compared to control animals. In contrast, these animals displayed significantly lower mRNA levels of ccl3 in BMS, relative to controls animals. Furthermore, the gene expression of cxcl16 was significantly upregulated in BMS after injection of animals with EPO. Together, LP and BMS showcase differential chemokine expression, suggesting that these distinct chemokines facilitate homing of different cell lineages to these respective frog tissues. Research to determine the specific cellular targets of these disparate chemokines will offer new insights into the mechanisms by which blood cell precursors are trafficked during distinct stages of hematopoiesis.

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