Chemokine Signaling

Sticking Together

Science Signaling  07 Oct 2008:
Vol. 1, Issue 40, pp. ec352
DOI: 10.1126/scisignal.140ec352

Gastrulation is the morphogenetic process by which the three germ layers of the vertebrate embryo are established and organized. As the body axis elongates, endoderm and mesoderm migrate together anteriorly, and their interaction affects the location and development of internal organs. Defects in endoderm affect development of mesodermal organs such as the heart and blood, and defects in the mesoderm affect endodermally derived organs such as the liver and pancreas. Nair and Schilling report that endodermal and mesodermal defects are genetically separable and that chemokine signaling plays a vital role in endodermal migration. Injecting zebrafish embryos with morpholino oligonucleotides targeting the chemokine Cxcl12b, which is expressed in the mesoderm, or its receptor Cxcr4a, which is expressed in the endoderm, resulted in duplication of the liver or pancreas, or both, but caused no defects in mesodermal organs. Quantitative reverse transcription polymerase chain reaction (RT-PCR) revealed that integrin expression in the endoderm of cxcr4a morphants was decreased relative to wild type, and injection of mRNA encoding integrin β rescued the duplicated organ phenotype of cxcl12b and cxcr4a morphants. In the absence of chemokine signaling, integrin-mediated cell adhesion was compromised, causing the endoderm to separate from the mesoderm and migrate farther anteriorly than normal, thus delaying the coalescence of the right and left sides of the endoderm and resulting in duplication of endodermal organs. The authors propose that chemokine signaling induces the integrin-mediated adhesion that coordinates migration of the mesoderm and endoderm and restricts the anterior migration of the endoderm.

S. Nair, T. F. Schilling, Chemokine signaling controls endodermal migration during zebrafish gastrulation. Science 322, 89-92 (2008). [Abstract] [Full Text]