β1-integrin controls cell fate specification in early lens development.
Integrins are heterodimeric cell surface molecules that mediate cell-extracellular matrix (ECM) adhesion, ECM assembly, and regulation of both ECM and growth factor induced signaling. However, the developmental context of these diverse functions is not clear. Loss of β1-integrin from the lens vesicle (mouse E10.5) results in abnormal exit of anterior lens epithelial cells (LECs) from the cell cycle and their aberrant elongation toward the presumptive cornea by E12.5. These cells lose expression of LEC markers and initiate expression of the Maf (also known as c-Maf) and Prox1 transcription factors as well as other lens fiber cell markers. β1-integrin null LECs also upregulate the ERK, AKT and Smad1/5/8 phosphorylation indicative of BMP and FGF signaling. By E14.5, β1-integrin null lenses have undergone a complete conversion of all lens epithelial cells into fiber cells. These data suggest that shortly after lens vesicle closure, β1-integrin blocks inappropriate differentiation of the lens epithelium into fibers, potentially by inhibiting BMP and/or FGF receptor activation. Thus, β1-integrin has an important role in fine-tuning the response of the early lens to the gradient of growth factors that regulate lens fiber cell differentiation.
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Mallika
M
Pathania
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Yan
Y
Wang
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Vladimir N
VN
Simirskii
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA. Electronic address: duncanm@udel.edu.
Melinda K
MK
Duncan
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D019012:Integrin beta1 / Q000235:genetics* / Q000378:metabolism; D007908:Lens, Crystalline / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D038081:Organogenesis / Q000235:genetics*; D051257:Proto-Oncogene Proteins c-maf / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D000098551:Prospero-Related Homeobox 1 Protein
D018398:Homeodomain Proteins; D019012:Integrin beta1; C495608:Maf protein, mouse; D051257:Proto-Oncogene Proteins c-maf; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein
BMP; FGF; Growth factor; Integrin; Lens fiber cell