pygopus 2 has a crucial, Wnt pathway-independent function in lens induction.
Drosophila Pygopus was originally identified as a core component of the canonical Wnt signaling pathway and a transcriptional coactivator. Here we have investigated the microophthalmia that arises in mice with a germline null mutation of pygopus 2. We show that this phenotype is a consequence of defective lens development at inductive stages. Using a series of regionally limited Cre recombinase transgenes for conditional deletion of Pygo2(flox), we show that Pygo2 activity in pre-placodal presumptive lens ectoderm, placodal ectoderm and ocular mesenchyme all contribute to lens development. In each case, Pygo2 is required for normal expression levels of the crucial transcription factor Pax6. Finally, we provide multiple lines of evidence that although Pygo2 can function in the Wnt pathway, its activity in lens development is Wnt pathway-independent.
Song
Ni
N
Divisions of Pediatric Ophthalmology, Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.
Schwab
Kristopher R
KR
Patterson
Larry T
LT
Yamaguchi
Terry
T
Lin
Xinhua
X
Potter
Steven S
SS
Lang
Richard A
RA
D000483:Alleles; D000818:Animals; D005136:Eye Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D007908:Lens, Crystalline / Q000196:embryology*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008957:Models, Genetic; D009432:Neural Crest / Q000166:cytology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D010641:Phenotype; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
D005136:Eye Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D051153:Wnt Proteins; C495570:pygopus 2 protein, mouse