Human DYRK1A is one of the crucial genes within the Down’s syndrome critical region of human chromosome 21. DYRK1A has been implicated in neuronal development and neurodegenerative disorders, but its roles in the brain vascular development is not clear. Here we generated a zebrafish knockout mutant for dyrk1aa gene (dyrk1aakbr1), one of the two zebrafish orthologues of mammalian DYRK1A, using the TAL endonuclease technique. Approximately 30% of the length and branching points of the central arteries (CtAs) situated in the hindbrain were reduced in dyrk1aakbr1 at 52hpf compared to the wild type (wt) control. Consistently, similar vascular defects were observed in a dose-dependent manner upon the treatment of harmine, a well-characterized DYRK1A inhibitor, while forced expression of dyrk1aa mRNA rescued CtA defects of dyrk1aakbr1. Overexpression of dyrk1aa mRNA in the wt background led to the increased length and branching points of CtAs, corroborating the role of dyrk1aa in promoting vascular formation in the developing brain. Currently we investigate the involvement of signaling pathways important for the dyrk1aa-regulated cerebrovascular development by examining expression patterns of candidate target genes and exploiting reporter transgenic lines. This study will reveal underappreciated roles of dyrk1aa in the vascular formation during cerebral development, and shed light on the vascular pathology in DYRK1A-related diseases including Down syndrome and Alzheimer’s disease. .