BACKGROUND: Transcription factors are critical in regulating lens development. The AP-2 family of transcription factors functions in differentiation, cell growth and apoptosis, and in lens and eye development. AP-2α, in particular, is important in early lens development, and when conditionally deleted at the placode stage defective separation of the lens vesicle from the surface ectoderm results. AP-2α's role during later stages of lens development is unknown. To address this, the MLR10-Cre transgene was used to delete AP-2α from the lens epithelium beginning at embryonic day (E) 10.5. RESULTS: The loss of AP-2α after lens vesicle separation resulted in morphological defects beginning at E18.5. By P4, a small highly vacuolated lens with a multilayered epithelium was evident in the MLR10-AP-2α mutants. Epithelial cells appeared elongated and expressed fiber cell specific βB1 and γ-crystallins. Epithelial cell polarity and lens cell adhesion was disrupted and accompanied by the misexpression of ZO-1, N-Cadherin, and β-catenin. Cell death was observed in the mutant lens epithelium between postnatal day (P) 14 and P30, and correlated with altered arrangements of cells within the epithelium. CONCLUSIONS: Our findings demonstrate that AP-2α continues to be required after lens vesicle separation to maintain a normal lens epithelial cell phenotype and overall lens integrity and to ensure correct fiber cell differentiation.
BACKGROUND: Transcription factors are critical in regulating lens development. The AP-2 family of transcription factors functions in differentiation, cell growth and apoptosis, and in lens and eye development. AP-2α, in particular, is important in early lens development, and when conditionally deleted at the placode stage defective separation of the lens vesicle from the surface ectoderm results. AP-2α's role during later stages of lens development is unknown. To address this, the MLR10-Cre transgene was used to delete AP-2α from the lens epithelium beginning at embryonic day (E) 10.5. RESULTS: The loss of AP-2α after lens vesicle separation resulted in morphological defects beginning at E18.5. By P4, a small highly vacuolated lens with a multilayered epithelium was evident in the MLR10-AP-2α mutants. Epithelial cells appeared elongated and expressed fiber cell specific βB1 and γ-crystallins. Epithelial cell polarity and lens cell adhesion was disrupted and accompanied by the misexpression of ZO-1, N-Cadherin, and β-catenin. Cell death was observed in the mutant lens epithelium between postnatal day (P) 14 and P30, and correlated with altered arrangements of cells within the epithelium. CONCLUSIONS: Our findings demonstrate that AP-2α continues to be required after lens vesicle separation to maintain a normal lens epithelial cell phenotype and overall lens integrity and to ensure correct fiber cell differentiation.
Authors: Ohad Shaham; April N Smith; Michael L Robinson; Makoto M Taketo; Richard A Lang; Ruth Ashery-Padan Journal: Development Date: 2009-07-01 Impact factor: 6.868
Authors: Rupalatha Maddala; Bharesh K Chauhan; Christopher Walker; Yi Zheng; Michael L Robinson; Richard A Lang; Ponugoti V Rao Journal: Dev Biol Date: 2011-09-16 Impact factor: 3.582
Authors: Charlene Rivera; Idella F Yamben; Shalini Shatadal; Malinda Waldof; Michael L Robinson; Anne E Griep Journal: Dev Dyn Date: 2009-09 Impact factor: 3.780
Authors: Judith A West-Mays; Jeremy M Sivak; Steve S Papagiotas; Jennifer Kim; Timothy Nottoli; Trevor Williams; M Elizabeth Fini Journal: Differentiation Date: 2003-04 Impact factor: 3.880