Coiled‐coil domain containing protein 103 regulates myeloid development and function

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Rationale Abnormal myeloid function is implicated in many diseases, including leukemia, atherosclerosis and others. Therefore, understanding regulators of myelopoiesis and myeloid function will lead to novel therapies. We have identified that the poorly understood coiled‐coil domain containing protein 103 (Ccdc103) is expressed in human and zebrafish myeloid cells. Objective The goal of this project is to test the hypothesis that Ccdc103 is a novel regulator of myeloid development and function. Methods and Results Ccdc103 is known to be involved in cilia motility and dynein arm assembly through direct interactions with microtubules. However , we found previously unrecognized expression of Ccdc103 in zebrafish and human myeloid progenitor cells. Furthermore, CCDC103 is expressed in highly proliferative myeloid leukemia cell lines and proliferative cultured myeloid progenitors, suggesting Ccdc103 may promote proliferation. Consistent with the hypothesis that Ccdc103 is involved in myeloid production, there are decreased and increased neutrophils and macrophages, respectively, in ccdc103 mutant and ccdc103 overexpressed zebrafish embryos. In addition to the defects in myeloid cell number, we found that Ccdc103 deficient embryos display abnormal myeloid progenitor cell migration, with myeloid progenitor cells migrating inappropriately from the anterior blood island. To further test the idea that Ccdc103 plays a role in myeloid migration, we performed in vivo wounding assays in zebrafish embryos at 24 hours post fertilization. We find that Ccdc103 deficient neutrophils and macrophages have a reduced ability to directly migrate to the wound and have abnormal macrophage morphology. Conclusion(s Altogether, our results indicate that Ccdc103 has functions outside of cells with motile cilia as a novel regulator of myeloid production and directed migration, indicating it or processes it regulates may be exciting targets for confronting myeloid‐related cardiovascular disorders. Support or Funding Information R01 HL112893 to JSW. NIH T32 Understanding of Cardiovascular Disease Mechanisms to SAB.

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