CXCR4 Regulates Branching Morphogenesis in Developing Epithelial Organ

The CXC Chemokine receptor type 4 (CXCR4), a member of 7-transmembrane receptor family, is known to facilitate migration of immune cells as well as stem cell homeostasis. Not only that, CXCR4 has gained extensive attention due to its ambivalent augmentation effects on the development of organs. Many studies have been conducted on the contributions of CXCR4 to organogenesis and, specifically, to neurogenesis and angiogenesis. However, the function of CXCR4 in the early branching stages of embryo submandibular gland is yet to be explored. In this study, we investigated the relations between CXCR4 and glandular branching morphogenesis. AMD3100, a potent CXCR4 inhibitor, was applied to embryo submandibular glands extracted from E13 and E14 embryos. E14 eSMGs showed a retarded growth compared to control group whereas the branching and expansion were nearly abolished in E13 eSMGs. Both control and AMD3100-treated groups, however, showed no significant difference in their expressions of cleaved caspase-3. Analysis of mRNA sequencing data revealed considerable increase in the expressions of acinar and ductal progenitor as well as of differentiation marker genes. Collectively, our results show that CXCR4 regulates the differentiation of acinar and ductal cells in glandular branching morphogenesis.