Netrin-1 and its receptors play an essential role patterning the nervous system by guiding neurons and axons to their targets. To explore whether netrin-1 organizes nonneural tissues, we examined its role in mammary gland morphogenesis. Netrin-1 is expressed in prelumenal cells, and its receptor neogenin is expressed in a complementary pattern in adjacent cap cells of terminal end buds (TEBs). We discovered that loss of either gene results in disorganized TEBs characterized by exaggerated subcapsular spaces, breaks in basal lamina, dissociated cap cells, and an increased influx of cap cells into the prelumenal compartment. Cell aggregation assays demonstrate that neogenin mediates netrin-1-dependent cell clustering. Thus, netrin-1 appears to act locally through neogenin to stabilize the multipotent progenitor (cap) cell layer during mammary gland development. Our results suggest that netrin-1 and its receptor neogenin provide an adhesive, rather than a guidance, function during nonneural organogenesis.
Pubmed ID: 12636918 RIS Download
Mesh terms: Actins | Animals | Apoptosis | Basement Membrane | Cadherins | Cell Adhesion | Cell Communication | Cell Differentiation | Cells, Cultured | Epithelial Cells | Female | Gene Expression Regulation, Developmental | Laminin | Mammary Glands, Animal | Membrane Proteins | Mice | Mice, Knockout | Mice, Nude | Multipotent Stem Cells | Nerve Growth Factors | Stem Cell Transplantation | Stem Cells | Tumor Suppressor Proteins
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