Functional Disruption of Netrin-1 Guidance Cue Leads to Disruption in Mammary Gland Development and Increased Tumor Incidence
Abstract
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 non-neural tissues, we examined its role in mammary gland morphogenesis. We hypothesized that netrin-1 regulates cell interactions during mammary gland development and that loss of this activity plays a role in mammary tumor formation. During this funding period, we discovered that netrin-1 is expressed in mammary gland prelumenal cells and its receptor, neogenin, in a complementary pattern in adjacent cap cells of terminal end buds. We discovered that loss of either gene results in disorganized terminal end buds 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 guidance function during non-neural organogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418357
Entities
People
- Lindsay Hinck
Organizations
- University of California, Santa Cruz