Cell autonomous roles for AP-2alpha in lens vesicle separation and maintenance of the lens epithelial cell phenotype.
In this study, we have created a conditional deletion of AP-2alpha in the developing mouse lens (Le-AP-2alpha mutants) to determine the cell-autonomous requirement(s) for AP-2alpha in lens development. Embryonic and adult Le-AP-2alpha mutants exhibited defects confined to lens placode derivatives, including a persistent adhesion of the lens to the overlying corneal epithelium (or lens stalk). Expression of known regulators of lens vesicle separation, including Pax6, Pitx3, and Foxe3 was observed in the Le-AP-2alpha mutant lens demonstrating that these genes do not lie directly downstream of AP-2alpha. Unlike germ-line mutants, Le-AP-2alpha mutants did not exhibit defects in the optic cup, further defining the tissue specific role(s) for AP-2alpha in eye development. Finally, comparative microarray analysis of lenses from the Le-AP-2alpha mutants vs. wild-type littermates revealed differential expression of 415 mRNAs, including reduced expression of genes important for maintaining the lens epithelial cell phenotype, such as E-cadherin.
Pontoriero
Giuseppe F
GF
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Deschamps
Paula
P
Ashery-Padan
Ruth
R
Wong
Ryan
R
Yang
Ying
Y
Zavadil
Jiri
J
Cvekl
Ales
A
Sullivan
Shelley
S
Williams
Trevor
T
West-Mays
Judith A
JA
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D005123:Eye / Q000196:embryology*; D005136:Eye Proteins / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D007908:Lens, Crystalline / Q000196:embryology*; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D015820:Cadherins; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; C498612:Foxe3 protein, mouse; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; C433629:homeobox protein PITX3