JCB logo
amgmicro.com
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 964K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tang, M.-J.
Right arrow Articles by Dressler, G. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tang, M.-J.
Right arrow Articles by Dressler, G. R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/1998//1337 $5.00
The Journal of Cell Biology, Volume 142, Number 5, , 1998 1337-1345

Articles

The RET–Glial Cell-derived Neurotrophic Factor (GDNF) Pathway Stimulates Migration and Chemoattraction of Epithelial Cells



Ming-Jer Tang*, Dane Worley{ddagger}, Michele Sanicola{ddagger}, and Gregory R. Dressler*

* Department of Pathology and Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan 48109; and {ddagger} Biogen, Inc., Cambridge, Massachusetts 02142

Embryonic development requires cell migration in response to positional cues. Yet, how groups of cells recognize and translate positional information into morphogenetic movement remains poorly understood. In the developing kidney, the ureteric bud epithelium grows from the nephric duct towards a group of posterior intermediate mesodermal cells, the metanephric mesenchyme, and induces the formation of the adult kidney. The secreted protein GDNF and its receptor RET are required for ureteric bud outgrowth and subsequent branching. However, it is unclear whether the GDNF–RET pathway regulates cell migration, proliferation, survival, or chemotaxis. In this report, we have used the MDCK renal epithelial cell line to show that activation of the RET pathway results in increased cell motility, dissociation of cell adhesion, and the migration towards a localized source of GDNF. Cellular responses to RET activation include the formation of lamellipodia, filopodia, and reorganization of the actin cytoskeleton. These data demonstrate that GDNF is a chemoattractant for RET-expressing epithelial cells and thus account for the developmental defects observed in RET and GDNF mutant mice. Furthermore, the RET-transfected MDCK cells described in this report are a promising model for delineating RET signaling pathways in the renal epithelial cell lineage.

Key Words: GDNF • RET • kidney development • chemoattraction • MDCK cells

Abbreviations used in this paper: CMV, cytomegalovirus; GDNF, glial cell-derived neurotrophic factor; GFR{alpha}-1, GDNF family receptor {alpha}-1; HA, hemagglutinin; HGF, hepatocyte growth factor; KM cells, kinase-deficient mutant cells; pTyr, phosphotyrosine.

Address all correspondence to G.R. Dressler, Department of Pathology, HHMI, University of Michigan, Ann Arbor, MI 48109. Tel.: (734) 764-6532. Fax: (734) 763-6640. E-mail: dressler{at}umich.edu

M.-J. Tang is on leave from the Department of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents