Conditional inactivation of the E-cadherin gene in thyroid follicular cells affects gland development but does not impair junction formation.
We have conditionally inactivated the E-cadherin gene in the thyroid follicular cells of mouse embryo to unravel its role in thyroid development. We used the Cre-loxP system in which the Cre-recombinase was expressed under the control of the tissue-specific thyroglobulin promoter that becomes active at embryonic d 15. At postnatal d 7, thyroid follicle lumens in the knockout mice were about 30% smaller with respect to control mice and had an irregular shape. E-cadherin was almost completely absent in thyrocytes, beta-catenin was significantly reduced, whereas no change in gamma-catenin was detected. alpha-Catenin was also reduced on the cell plasma membrane. Despite the dramatic loss of E-cadherin and beta-catenin, cell-cell junctions were not affected, the distribution of tight junction proteins was unaltered, and no increase of thyroglobulin circulating in the blood was observed. In addition, we found that other members of the cadherin family, the R-cadherin and the Ksp-cadherin, were expressed in thyrocytes and that their membrane distribution was not altered in the E-cadherin conditional knockout mouse. Our results indicate that E-cadherin has a role in the development of the thyroid gland and in the expression of beta-catenin, but it is not essential for the maintenance of follicular cell adhesion.
Calì
Gaetano
G
Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Richerche, 80131 Naples, Italy.
Zannini
Mariastella
M
Rubini
Patrizia
P
Tacchetti
Carlo
C
D'Andrea
Barbara
B
Affuso
Andrea
A
Wintermantel
Tim
T
Boussadia
Oreda
O
Terracciano
Daniela
D
Silberschmidt
Daniel
D
Amendola
Elena
E
De Felice
Mario
M
Schütz
Günther
G
Kemler
Rolf
R
Di Lauro
Roberto
R
Nitsch
Lucio
L
D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000235:genetics; D062445:Claudin-1; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D011247:Pregnancy; D013961:Thyroid Gland / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism*; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D015820:Cadherins; D062445:Claudin-1; C568113:Cldn1 protein, mouse; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin