Gata2 is an essential hematopoietic transcriptional factor that is also expressed prominently in the nervous system. The early lethality of knockout mice due to severe anemia has largely precluded studies of gata2 neural regulation and function. In this report, we describe the identification of zebrafish Pur alpha and Sp8 orthologs as two factors that function to regulate neuronal expression of gata2. During embryogenesis, Pur alpha is expressed widely, whereas Sp8 has an overlapping pattern of expression with gata2 in the nervous system. Knockdown and ectopic expressions of Pur alpha and Sp8 indicate that these factors function, respectively, as a repressor and an activator of gata2 gene expression in the nervous system. With consideration given to the previously established roles for these factors, we propose a model for how the transcriptional regulation of neural gata2 expression may be involved in controlling cellular proliferation in the nervous system.