Modulation of N-cadherin junctions and their role as epicenters of differentiation-specific actin regulation in the developing lens.
Extensive elongation of lens fiber cells is a central feature of lens morphogenesis. Our study investigates the role of N-cadherin junctions in this process in vivo. We investigate both the molecular players involved in N-cadherin junctional maturation and the subsequent function of these junctions as epicenters for the assembly of an actin cytoskeleton that drives morphogenesis. We present the first evidence of nascent cadherin junctions in vivo, and show that they are a prominent feature along lateral interfaces of undifferentiated lens epithelial cells. Maturation of these N-cadherin junctions, required for lens cell differentiation, preceded organization of a cortical actin cytoskeleton along the cells' lateral borders, but was linked to recruitment of α-catenin and dephosphorylation of N-cadherin-linked β-catenin. Biochemical analysis revealed differentiation-specific recruitment of actin regulators cortactin and Arp3 to maturing N-cadherin junctions of differentiating cells, linking N-cadherin junctional maturation with actin cytoskeletal assembly during fiber cell elongation. Blocking formation of mature N-cadherin junctions led to reduced association of α-catenin with N-cadherin, prevented organization of actin along lateral borders of differentiating lens fiber cells and blocked their elongation. These studies provide a molecular link between N-cadherin junctions and the organization of an actin cytoskeleton that governs lens fiber cell morphogenesis in vivo.
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Michelle
M
Leonard
Liping
L
Zhang
Ni
N
Zhai
Ahmad
A
Cader
Yim
Y
Chan
Roberta B
RB
Nowak
Velia M
VM
Fowler
A Sue
AS
Menko
D000199:Actins / Q000378:metabolism*; D022005:Adherens Junctions / Q000502:physiology*; D000818:Animals; D015820:Cadherins / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002642:Chick Embryo; D003599:Cytoskeleton / Q000378:metabolism / Q000502:physiology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D007908:Lens, Crystalline / Q000166:cytology / Q000196:embryology*; D008856:Microscopy, Fluorescence; D009024:Morphogenesis / Q000502:physiology*; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism; D051178:alpha Catenin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D000199:Actins; D015820:Cadherins; D051178:alpha Catenin; D051176:beta Catenin; D014443:Tyrosine