spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sudarsan, V.
Right arrow Articles by Skaer, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sudarsan, V.
Right arrow Articles by Skaer, H.
Development 129, 935-944 (2002)
© 2002 The Company of Biologists Limited

A genetic hierarchy establishes mitogenic signalling and mitotic competence in the renal tubules of Drosophila

Vikram Sudarsan1,*, Sara Pasalodos-Sanchez1,*, Susan Wan1, Alexandra Gampel2 and Helen Skaer1,*,{dagger}

1 Centre for Developmental Genetics, BMS, University of Sheffield, UK, S10 2TN
2 Department of Biochemistry, University of Bristol, UK, BS8 1TD
* Present address: Department of Zoology, Downing Street, Cambridge, UK, CB2 3EJ

{dagger}Author for correspondence (e-mail: hs17{at}cam.ac.uk)

Accepted 29 November 2001

Cell proliferation in the developing renal tubules of Drosophila is strikingly patterned, occurring in two phases to generate a consistent number of tubule cells. The later phase of cell division is promoted by EGF receptor signalling from a specialised subset of tubule cells, the tip cells, which express the protease Rhomboid and are thus able to secrete the EGF ligand, Spitz. We show that the response to EGF signalling, and in consequence cell division, is patterned by the specification of a second cell type in the tubules. These cells are primed to respond to EGF signalling by the transcription of two pathway effectors, PointedP2, which is phosphorylated on pathway activation, and Seven up. While expression of pointedP2 is induced by Wingless signalling, seven up is initiated in a subset of the PointedP2 cells through the activity of the proneural genes. We demonstrate that both signalling and responsive cells are set aside in each tubule primordium from a proneural gene-expressing cluster of cells, in a two-step process. First, a proneural cluster develops within the domain of Wingless-activated, pointedP2-expressing cells to initiate the co-expression of seven up. Second, lateral inhibition, mediated by the neurogenic genes, acts within this cluster of cells to segregate the tip cell precursor, in which proneural gene expression strengthens to initiate rhomboid expression. As a consequence, when the precursor cell divides, both daughters secrete Spitz and become signalling cells. Establishing domains of cells competent to transduce the EGF signal and divide ensures a rapid and reliable response to mitogenic signalling in the tubules and also imposes a limit on the extent of cell division, thus preventing tubule hyperplasia.

Key words: Cell division, Malpighian tubules, Proneural genes, EGFR signalling, seven up, wingless, Drosophila






© The Company of Biologists Ltd 2002