The Sp1-related transcription factors sp5 and sp5-like act downstream of Wnt/beta-catenin signaling in mesoderm and neuroectoderm patterning

Curr Biol. 2005 Mar 29;15(6):489-500. doi: 10.1016/j.cub.2005.01.041.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning / physiology*
  • Cloning, Molecular
  • Cytoskeletal Proteins / metabolism
  • Ectoderm / physiology*
  • Gene Expression Regulation, Developmental*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Luciferases
  • Mesoderm / physiology*
  • Oligonucleotide Array Sequence Analysis
  • Oligonucleotides
  • Rhombencephalon / embryology
  • Signal Transduction / physiology*
  • Trans-Activators / metabolism*
  • Wnt Proteins
  • Zebrafish / embryology*
  • Zebrafish Proteins / metabolism*
  • beta Catenin


  • Cytoskeletal Proteins
  • Intercellular Signaling Peptides and Proteins
  • Oligonucleotides
  • Trans-Activators
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin
  • ctnnb1 protein, zebrafish
  • sp5a protein, zebrafish
  • Luciferases