N-cadherin is dispensable for pancreas development but required for beta-cell granule turnover.
The cadherin family of cell adhesion molecules mediates adhesive interactions that are required for the formation and maintenance of tissues. Previously, we demonstrated that N-cadherin, which is required for numerous morphogenetic processes, is expressed in the pancreatic epithelium at E9.5, but later becomes restricted to endocrine aggregates in mice. To study the role of N-cadherin during pancreas formation and function we generated a tissue-specific knockout of N-cadherin in the early pancreatic epithelium by inter-crossing N-cadherin-floxed mice with Pdx1Cre mice. Analysis of pancreas-specific ablation of N-cadherin demonstrates that N-cadherin is dispensable for pancreatic development, but required for beta-cell granule turnover. The number of insulin secretory granules is significantly reduced in N-cadherin-deficient beta-cells, and as a consequence insulin secretion is decreased.
Johansson
Jenny K
JK
Stem Cell Center, Department of Laboratory Medicine, Lund University, Sweden.
Voss
Ulrikke
U
Kesavan
Gokul
G
Kostetskii
Igor
I
Wierup
Nils
N
Radice
Glenn L
GL
Semb
Henrik
H
D000818:Animals; D015820:Cadherins / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology*; D015151:Immunoblotting; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000254:growth & development* / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*
D015820:Cadherins; C489083:Cdh2 protein, mouse; D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; C045073:Cre recombinase; D019426:Integrases