The Sp1-Related Transcription Factors sp5 and sp5-like Act Downstream of Wnt/beta-Catenin Signaling in Mesoderm and Neuroectoderm Patterning

Background: Wnt/beta-catenin signaling regulates many processes during vertebrate development, including patterning of the mesoderm along the dorso-ventral axis and patterning of the neuroectoderm along the anterior-posterior axis during gastrulation. However, relatively little is known about Wnt target genes mediating these effects. Results: Using zebrafish DNA microarrays, we have identified several new targets of Wnt/beta-catenin signaling, including sp5-like (sp5l, previously called spr2), a zinc-finger transcription factor of the Sp1 family. sp5-like is a direct target of Wnt/beta-catenin signaling and acts together with its paralog sp5 (previously called bts1) downstream of wnt8 in patterning of the mesoderm and neuroectoderm because (1) overexpression of sp5-like, like overexpression of wnt8, posteriorizes the neuroectoderm, (2) sp5-like morpholino-mediated knockdown, like wnt8 knockdown, causes anteriorization of the hindbrain, (3) combined knockdown of sp5 and sp5-like, like loss of wnt8, causes expansion of dorsal mesoderm, (4) sp5-like knockdown reduces the defects in mesoderm and neuroectoderm patterning caused by wnt8 overexpression, and (5) inhibition of sp5-like enhances the effects of hypomorphic loss of wnt8. Importantly, (6) overexpression of sp5-like is able to partially restore normal hindbrain patterning in wnt8 morphants. Conclusions:sp5-like is a direct target of Wnt/beta-catenin signaling during gastrulation and, together with sp5, acts as a required mediator of the activities of wnt8 in patterning the mesoderm and neuroectoderm. We conclude that sp5 transcription factors mediate the downstream responses to Wnt/beta-catenin signaling in several developmental processes in zebrafish.