Developmental phenotypes and reduced Wnt signaling in mice deficient for pygopus 2.
Canonical Wnt signaling involves complex intracellular events culminating in the stabilization of beta-catenin, which enters the nucleus and binds to LEF/TCF transcription factors to stimulate gene expression. Pygopus was identified as a genetic modifier of Wg (Wnt homolog) signaling in Drosophila, and encodes a PHD domain protein that associates with the beta-catenin/LEF/TCF complex. Two murine pygopus paralogs, mpygo1 and mpygo2, have been identified, but their roles in development and Wnt signaling remain elusive. In this study, we report that ablation of mpygo2 expression in mice causes defects in morphogenesis of both ectodermally and endodermally derived tissues, including brain, eyes, hair follicles, and lung. However, no gross abnormality was observed in embryonic intestine. Using a BAT-gal reporter, we found Wnt signaling at most body sites to be reduced in the absence of mpygo2. Taken together, our studies show for the first time that mpygo2 deletion affects embryonic development of some but not all Wnt-requiring tissues.
Li
Boan
B
Department of Biological Chemistry, University of California, Irvine, California 92697-1700, USA.
Rhéaume
Catherine
C
Teng
Andy
A
Bilanchone
Virginia
V
Munguia
Jesus E
JE
Hu
Ming
M
Jessen
Shannon
S
Piccolo
Stefano
S
Waterman
Marian L
ML
Dai
Xing
X
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009928:Organ Specificity; D010641:Phenotype; D011247:Pregnancy; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D051153:Wnt Proteins; C495570:pygopus 2 protein, mouse