We have characterized a cDNA clone, rdd (repeated D domain-like), that encodes for a secretory protein consisting of repeated domains of cysteine-rich sequence. Whole-mount in situ hybridization analysis revealed that rdd2, rdd3 and rdd4 are transiently expressed in the ventral and lateral mesoderm and the overlying ectoderm at the late gastrula and tailbud stages. Morpholino oligonucleotide (MO) was used to inhibit the translation of endogenous rdd3 and rdd4, and we found that the circulation of red blood cells completely disappears in the MO-injected tadpoles. Histological analysis showed that formation of the ventral aorta, dorsal aorta and posterior cardinal vein in the trunk region was severely disorganized in these animals. injection of MO affected the expression of alpha-globin, a terminal differentiation marker of red blood cells, but did not affect the expression of scl, flk-1 or tie-2, suggesting that angiopoietic and hematopoietic precursor cells differentiate normally in the rdd-depleted embryo. The transplantation of labeled tissues followed by tracing of the donor cells revealed a role of rdds in migration of the embryonic angioblasts and myeloid cells. These observations first demonstrate the role of the novel cysteine-rich proteins in migration of the embryonic cells. (C) 2007 Elsevier Ireland Ltd. All rights reserved.