QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online January 16, 2009
Journal of Experimental Biology 212, 413-423 (2009)
Published by The Company of Biologists 2009
doi: 10.1242/jeb.024216

This Article Summary Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JEB Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Singh, S. R. Articles by Hou, S. X. Search for Related Content PubMed Articles by Singh, S. R. Articles by Hou, S. X. Social Bookmarking                         What's this?

Multipotent stem cells in the Malpighian tubules of adult Drosophila melanogaster

Shree Ram Singh and Steven X. Hou^*

Mouse Cancer Genetics Program, National Institutes of Health, National Cancer Institute at Frederick, Frederick, MD 21702, USA

View larger version (21K): [in this window] [in a new window]   Fig. 1. Proposed model of mammalian kidney development and the origin of tubular epithelial regenerating cells after acute renal injury. MM, metanephric mesenchyme; UB, ureteric bud; MET, mesenchymal-to-epithelial transition; BM, bone marrow; HSC, hematopoietic stem cells; MSC, mesenchymal stem cells.

View larger version (60K): [in this window] [in a new window]   Fig. 2. The Malpighian tubules (MTs) and renal stem cell lineage in Drosophila. (A) Drawing of the Drosophila MTs (modified from Wessing and Eichelberg, 1978). The adult MTs consist of two pairs of epithelial tubes: a longer, anterior pair runs through the hemolymph on both sides of the midgut, and a shorter, posterior pair runs along the hindgut. The pairs converge at a common ureter at the midgut–hindgut junction. Each tubule is divided into four compartments: initial, transitional, main and proximal (lower tubules and ureter). (B–D) Expression pattern of unique molecular markers in the region of lower tubules and ureters of adult Drosophila MTs. (B) Kr-Gal4/UAS-GFP is specifically expressed in the small nuclear cells (anti-GFP, green; anti-Arm, red; DAPI, blue). (C) upd-Gal4/UAS-GFP expressed in the region of the lower tubules and ureters (anti-GFP, green; DAPI, blue). (D) Stat92E-GFP reporter is expressed only in small nuclear cells in the region of the lower tubules and ureters (anti-Arm, red; anti-GFP, green; DAPI, blue). (E–G) MTs with GFP-marked wild-type MARCM clones. (E) Six days after clone induction, GFP marks clusters of cells with small, intermediate and large nuclei in the region of the lower tubules and ureters. (F) An enlarged view of a GFP-marked clone from E [arrow, renal and nephric stem cells (RNSCs), anti-arm, red; anti-GFP, green; DAPI, blue]. (G) 10 days after clone induction in the upper tubule, the GFP labels both stellate and principal cells. (H) Schematic summary of renal and nephric stem cell lineage in Drosophila MTs (modified from Singh and Hou, 2008). Markers expressed in RNSCs, and their differentiated cells are shown in parentheses. RB, renalblast; RC, renalcyte. Scale bars, 10 µm (B–E), 5 µm (F–G).

View larger version (31K): [in this window] [in a new window]   Fig. 3. Schematic diagram of the JAK-STAT pathway. The components of JAK-STAT are: JAK, encoded by the hopscotch (hop) gene; STAT, encoded by the Stat92E (signal-transducer and activator of: transcription protein at 92E) gene; a ligand, encoded by the unpaired (upd) gene; a receptor, encoded by the domeless (dome)/Master of Marrelle (mom) gene; and negative regulators, Socs36E, ken and NURF. The activated Stat92E enters the nucleus to activate its target genes' transcription. Several other molecules interact and regulate the STAT activity, such as cyclin D (cycD-Cdk4), cyclin E (CycE-Cdk2), and the Drosophila homolog of BHD.

View larger version (26K): [in this window] [in a new window]   Fig. 4. Schematic summary of genes regulating renal cell carcinoma (RCC) in mammalian kidney. Kidney tissues are made up of many types of cells. These cells grow and divide in a controlled way to produce more cells as they are needed to keep the kidney healthy. When normal cells are damaged beyond repair, they are eliminated by apoptosis. When the genetic material of a cell is altered, cells avoid apoptosis and continue to multiply in an unregulated manner, accumulating mutations that affect normal cell growth and division and resulting in tumor formation. Model shows the renal tumors caused by mutation of the different genes. Renal progenitor cells are regulated by TSCs (tuberous sclerosis complex; TSC1 and TSC2) that are able to differentiate into either mesenchymal or epithelial cells. Mutations in TSC1 or TSC2 cause either mesenchymal (oncocytomas and cyst) or epithelial (angiomyolipomas) tumors. However, most of the common tumors are epithelial RCC type. RCC originates primarily in the proximal renal tubules and, rarely, in collecting ducts. These tumors are clear cell carcinoma, papillary, chromophobe or oncocytomas. Some of the tumors are of epithelial origin and are seen, only seen in children (Wilms' tumor); some of the tumors are also caused by the combination of both epithelial and stroma cells (transitional cell carcinomas).

View larger version (27K): [in this window] [in a new window]   Fig. 5. Proposed model of molecular pathways that regulate kidney tumors in mammals. See text for full names of proteins.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

Twitter