A single homeodomain binding site restricts spatial expression of Wnt-1 in the developing brain.
In this study we investigate the molecular mechanisms that are responsible for the restricted expression of Wnt-1 during embryogenesis. We report that a single homeodomain binding site, HBS1, within the Wnt-1 enhancer contributes to appropriate spatial expression of Wnt-1 in the developing nervous system. This HBS1 site may be required for repressing Wnt-1 expression in the developing forebrain since specific mutations of this site result in an extension of the rostral boundary of Wnt-1/lacZ staining in transgenic embryos. We further demonstrate that a subset of homeodomain proteins expressed in the forebrain (i.e., Dix2, Emx2) interact specifically with HBS1. These findings suggest that these (or related) homeodomain proteins may regulate expression of Wnt-1 during normal brain development by interacting with the HBS1 site in the Wnt-1 enhancer.
Iler
N
N
Center for Advanced Biotechnology and Medicine, Piscataway, NJ 08854, USA.
Rowitch
D H
DH
Echelard
Y
Y
McMahon
A P
AP
Abate-Shen
C
C
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D005314:Embryonic and Fetal Development / Q000235:genetics; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018390:Gene Targeting; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016548:Prosencephalon / Q000196:embryology / Q000378:metabolism*
D018398:Homeodomain Proteins