Eye-specific expression of an ancestral jellyfish PaxB gene interferes with Pax6 function despite its conserved Pax6/Pax2 characteristics.
Pax transcription factors are evolutionarily conserved regulators of eye development and can be distinguished on the basis of three functional domains: two DNA-binding domains (the paired domain and the paired-type homeodomain), and the octapeptide motif. PaxB of the eyed cubozoan jellyfish, Tripedalia cystophora, is characterized by a Pax2-like paired domain and octapeptide, and a Pax6-like homeodomain. In mice, functionally distinct Pax6 and Pax2 proteins have unique as well as redundant roles in eye morphogenesis. Here, we show that expression of the jellyfish PaxB gene in mouse embryonic eye tissues impairs normal development of lens and retina. Our data show that PaxB misexpression leads to a downregulation of endogenous Pax6 protein in the prospective lens and in subsets of cells within the inner nuclear layer of transgenic retina. In addition to Pax6 downregulation, the expression of PaxB leads to an almost complete loss of amacrine cells in the adult transgenic retina, a phenotype that differs from a loss-of-function of the Pax6 gene. The present data suggest that PaxB, due to its Pax2-like paired domain and Pax-6 like homeodomain, disturbs the transcriptional network regulated by Pax6 in the developing lens and retina. Taken together, our data suggest that molecular properties of individual mouse Pax2 and Pax6 proteins are essential determinants of mouse eye development and cannot be substituted for by jellyfish PaxB which possesses elements of vertebrate Pax2 and Pax6.
Ruzickova
Jana
J
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 142 20 Prague 4, Czech Republic.
Piatigorsky
Joram
J
Kozmik
Zbynek
Z
D000818:Animals; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005123:Eye / Q000196:embryology / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D037401:Scyphozoa / Q000235:genetics / Q000378:metabolism*
D005136:Eye Proteins; D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; D051762:PAX2 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins