ZFIN ID: ZDB-PUB-040914-5
Sp8 and Sp9, two closely related buttonhead-like transcription factors, regulate Fgf8 expression and limb outgrowth in vertebrate embryos
Kawakami, Y., Esteban, C.R., Matsui, T., Rodriguez-Leon, J., Kato, S., and Izpisúa Belmonte, J.C.
Date: 2004
Source: Development (Cambridge, England)   131(19): 4763-4774 (Journal)
Registered Authors: Izpisúa Belmonte, Juan Carlos, Kawakami, Yasuhiko, Matsui, Takaaki
Keywords: Apical ectodermal ridge, Sp transcription factor, Fgf8, Fgf10, Wnt, Vertebrate limb
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Chick Embryo
  • DNA, Complementary/genetics
  • DNA-Binding Proteins/genetics*
  • DNA-Binding Proteins/metabolism*
  • Evolution, Molecular
  • Extremities/embryology*
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors/genetics*
  • Fibroblast Growth Factors/metabolism*
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Mutation
  • Phylogeny
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins/metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Transcription Factors/genetics*
  • Transcription Factors/metabolism*
  • Wnt Proteins
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 15358670 Full text @ Development
Initiation and maintenance of signaling centers is a key issue during embryonic development. The apical ectodermal ridge, a specialized epithelial structure and source of Fgf8, is a pivotal signaling center for limb outgrowth. We show that two closely related buttonhead-like zinc-finger transcription factors, Sp8 and Sp9, are expressed in the AER, and regulate Fgf8 expression and limb outgrowth. Embryological and genetic analyses have revealed that Sp8 and Sp9 are ectodermal targets of Fgf10 signaling from the mesenchyme. We also found that Wnt/beta-catenin signaling positively regulates Sp8, but not Sp9. Overexpression functional analyses in chick unveiled their role as positive regulators of Fgf8 expression. Moreover, a dominant-negative approach in chick and knockdown analysis with morpholinos in zebrafish revealed their requirement for Fgf8 expression and limb outgrowth, and further indicate that they have a coordinated action on Fgf8 expression. Our study demonstrates that Sp8 and Sp9, via Fgf8, are involved in mediating the actions of Fgf10 and Wnt/beta-catenin signaling during vertebrate limb outgrowth.