N-cadherin is not essential for limb mesenchymal chondrogenesis.
The cell adhesion molecule N-cadherin is implicated in many morphogenetic processes, including mesenchyme condensation during limb development. To further understand N-cadherin function, we characterized a new N-cadherin allele containing the lacZ reporter gene under the regulation of the mouse N-cadherin promoter. The reporter gene recapitulates the expression pattern of the N-cadherin gene, including expression in heart, neural tube, and somites. In addition, strong expression was observed in areas of active cellular condensation, a prerequisite for chondrogenic differentiation, including the developing mandible, vertebrae, and limbs. Previous studies from our laboratory have shown that limb buds can form in N-cadherin-null embryos expressing a cardiac-specific cadherin transgene, however, these partially rescued embryos do not survive long enough to observe limb development. To overcome the embryonic lethality, we used an organ culture system to examine limb development ex vivo. We demonstrate that N-cadherin-deficient limb buds were capable of mesenchymal condensation and chondrogenesis, resulting in skeletal structures. In contrast to previous studies in chicken using N-cadherin-perturbing antibodies, our organ culture studies with mouse tissue demonstrate that N-cadherin is not essential for limb mesenchymal chondrogenesis. We postulate that another cell adhesion molecule, possibly cadherin-11, is responsible for chondrogenesis in the N-cadherin-deficient limb.
Luo
Yang
Y
Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Kostetskii
Igor
I
Radice
Glenn L
GL
D000423:Alcian Blue / Q000378:metabolism / Q000494:pharmacology; D000483:Alleles; D000818:Animals; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion; D020219:Chondrogenesis; D003433:Crosses, Genetic; D005121:Extremities / Q000196:embryology*; D019084:Fluorescent Antibody Technique, Indirect; D005697:Galactosides; D017930:Genes, Reporter; D005821:Genetic Techniques; D006579:Heterozygote; D006720:Homozygote; D007211:Indoles; D007763:Lac Operon; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009924:Organ Culture Techniques; D011401:Promoter Regions, Genetic; D012190:Retroviridae / Q000235:genetics; D020079:Terminal Repeat Sequences; D013997:Time Factors; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
D015820:Cadherins; D005697:Galactosides; D007211:Indoles; C086960:osteoblast cadherin; D001616:beta-Galactosidase; D000423:Alcian Blue; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside