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.
Weidinger
Gilbert
G
Howard Hughes Medical Institute, Department of Pharmacology and Center for Developmental Biology, University of Washington School of Medicine, Box 357370, Seattle, Washington 98195, USA.
Thorpe
Chris J
CJ
Wuennenberg-Stapleton
Katrin
K
Ngai
John
J
Moon
Randall T
RT
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004475:Ectoderm / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008156:Luciferases; D008648:Mesoderm / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides; D012249:Rhombencephalon / Q000196:embryology; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D051153:Wnt Proteins; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism*; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009841:Oligonucleotides; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C495269:ctnnb1 protein, zebrafish; C438751:sp5a protein, zebrafish; D008156:Luciferases