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First published online 26 January 2006
doi: 10.1242/dev.02261

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.02261v1 133/5/823    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Strickland, P. Articles by Hinck, L. Search for Related Content PubMed PubMed Citation Articles by Strickland, P. Articles by Hinck, L.

Slit2 and netrin 1 act synergistically as adhesive cues to generate tubular bi-layers during ductal morphogenesis

Phyllis Strickland^1,*, Grace C. Shin^1,*, Andrew Plump², Marc Tessier-Lavigne³ and Lindsay Hinck^1,

¹ Department of Molecular, Cell and Developmental Biology University of California, Santa Cruz Santa Cruz, CA 95064, USA.
² Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, New Jersey 07065, USA.
³ Genentech, Incorporated, 1 DNA Way, South San Francisco, CA 94080, USA.

Author for correspondence (e-mail: hinck{at}biology.ucsc.edu)

Accepted 21 December 2005

Development of many organs, including the mammary gland, involves ductal morphogenesis. Mammary ducts are bi-layered tubular structures comprising an outer layer of cap/myoepithelial cells (MECs) and an inner layer of luminal epithelial cells (LECs). Slit2 is expressed by cells in both layers, with secreted SLIT2 broadly distributed throughout the epithelial compartment. By contrast, Robo1 is expressed specifically by cap/MECs. Loss-of-function mutations in Slit2 and Robo1 yield similar phenotypes, characterized by disorganized end buds (EBs) reminiscent of those present in Ntn1^-/- glands, suggesting that SLIT2 and NTN1 function in concert during mammary development. Analysis of Slit2^-/-;Ntn1^-/- glands demonstrates an enhanced phenotype that extends through the ducts and is characterized by separated cell layers and occluded lumens. Aggregation assays show that Slit2^-/-;Ntn1^-/- cells, in contrast to wild-type cells, do not form bi-layered organoids, a defect rescued by addition of SLIT2. NTN1 has no effect alone, but synergistically enhances this rescue. Thus, our data establish a novel role for SLIT2 as an adhesive cue, acting in parallel with NTN1 to generate cell boundaries along ducts during bi-layered tube formation.

Key words: Slit, Robo, Netrin, Neogenin, Mammary, Mouse

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Ductal morphogenesis: new cues

Development 2006 133: e504. [Full Text]  

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