TY - JOUR
T1 - Contributions by members of the TGFbeta superfamily to lens development
AU - Beebe, David
AU - Garcia, Claudia
AU - Wang, Xiaohui
AU - Rajagopal, Ramya
AU - Feldmeier, Mary
AU - Kim, Ji Young
AU - Chytil, Anna
AU - Moses, Harold
AU - Ashery-Padan, Ruth
AU - Rauchman, Michael
PY - 2004
Y1 - 2004
N2 - Members of the TGFβ superfamily of growth and differentiation factors, including the TGFβ, BMP, activin and nodal families, play important signaling roles throughout development. This paper summarizes some of the functions of these ligands in lens development. Targeted deletion of the genes encoding one of the BMP receptors, Alk3 (BMP receptor-1A), showed that signaling through this receptor is essential for normal lens development. Lenses lacking Alk3 were smaller than smaller than normal, with thin epithelial layers. The fiber cells of Alk3 null lenses became vacuolated and degenerated within the first week after birth. Lenses lacking Alk3 function were surrounded by abnormal mesenchymal cells, suggesting that the lenses provided inappropriate signals to surrounding tissues. Lens epithelial and fiber cells contained endosomes that were associated with activated (phosphorylated) SMAD1 and SMAD2. Endosomal localization of pSMAD1 was reduced in the absence of Alk3 signaling. The presence of pSMAD2 in lens fiber cell nuclei and the observation that the activin antagonist follistatin inhibited lens cell elongation suggested that an activin-like molecule participates in lens fiber cell differentiation. Lenses deficient in type II TGFβ receptors were clear and had fiber cells of normal morphology. This suggests that TGFβ signaling is not essential for the normal differentiation of lens fiber cells. The targeted deletion of single or multiple receptors of the TGFβ superfamily in the lens should further characterize the role of these signaling molecules in lens development. This approach may also provide a useful way to define the downstream pathways that these are activated by these receptors during the development of the lens and other tissues.
AB - Members of the TGFβ superfamily of growth and differentiation factors, including the TGFβ, BMP, activin and nodal families, play important signaling roles throughout development. This paper summarizes some of the functions of these ligands in lens development. Targeted deletion of the genes encoding one of the BMP receptors, Alk3 (BMP receptor-1A), showed that signaling through this receptor is essential for normal lens development. Lenses lacking Alk3 were smaller than smaller than normal, with thin epithelial layers. The fiber cells of Alk3 null lenses became vacuolated and degenerated within the first week after birth. Lenses lacking Alk3 function were surrounded by abnormal mesenchymal cells, suggesting that the lenses provided inappropriate signals to surrounding tissues. Lens epithelial and fiber cells contained endosomes that were associated with activated (phosphorylated) SMAD1 and SMAD2. Endosomal localization of pSMAD1 was reduced in the absence of Alk3 signaling. The presence of pSMAD2 in lens fiber cell nuclei and the observation that the activin antagonist follistatin inhibited lens cell elongation suggested that an activin-like molecule participates in lens fiber cell differentiation. Lenses deficient in type II TGFβ receptors were clear and had fiber cells of normal morphology. This suggests that TGFβ signaling is not essential for the normal differentiation of lens fiber cells. The targeted deletion of single or multiple receptors of the TGFβ superfamily in the lens should further characterize the role of these signaling molecules in lens development. This approach may also provide a useful way to define the downstream pathways that these are activated by these receptors during the development of the lens and other tissues.
KW - Bone morphogenetic proteins
KW - Differentiation
KW - Endosomes
KW - Lens
KW - TGFβ superfamily
UR - http://www.scopus.com/inward/record.url?scp=19944386897&partnerID=8YFLogxK
U2 - 10.1387/ijdb.041869db
DO - 10.1387/ijdb.041869db
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AN - SCOPUS:19944386897
SN - 0214-6282
VL - 48
SP - 845
EP - 856
JO - International Journal of Developmental Biology
JF - International Journal of Developmental Biology
IS - 8-9
ER -