The Drosophila melanogaster Malpighian tubule
Confocal 3-D reconstructions of tubule-specific enhancer trap lines
(Ali Sozen/Douglas Armstrong).
Left: a subset of primary epithelial cells. Right: secondary, or "stellate",
cells. (Click either image to view a large (0.5 Mb) Quicktime movie.)
We are interested in applying the unique power of Drosophila molecular genetics to problems of ion transport and epithelial function. In collaboration with Kim Kaiser (Glasgow) and Simon Maddrell (Cambridge), we have established that the Drosophila Malpighian tubule is amenable to physiological, biochemical, molecular and genetic analysis.
We aim to identify the major transport and cell signalling genes involved in the function of this model epithelium, and then to intervene genetically to study their relative significance in physiological function. Uniquely among model epithelia, the beautiful genetic techniques developed by the Drosophila community will let us intervene in single tissues, or even single cell subtypes, within the tubules of the intact organism. This ability to manipulate the tissue in vivo gives the tubules an essential -and at present unique- qualification for the new integrative physiology.
Our "manifesto" is that there should be at least one model epithelium in biology which can be studied with this convergence of techniques, and that the Drosophila melanogaster tubule is it.
Shireen Davies (BBRSC Technology Foresight Fellow) Molecular genetics of the NO / cGMP signalling pathway in controlling fluid transport by Drosophila tubules.
Julian Dow Tubule transport physiology. Drosophila homologues of vertebrate transport and cell signalling genes. Knockouts and conditional mutants.
Angela Gawthrop Genetic analysis of Drosophila Integral Protein (DRIP), a member of the aquaporin family of small solute transporters.
Shirley Graham (in collaboration with Dr Malcolm Finbow, CRC
Beatson Institute for Cancer Research)
Mutagenesis of the gene encoding the16 kDa proteolipid subunit of the V-ATPase.
Genetic dissection of roles in endomembrane vesicle acidification, plasma
membrane epithelial function and cell communication.
Phillipe Rosay Analysis of calcium signalling in Drosophila using aequorin transgenes.
Dr Julian A.T. Dow
Division of Molecular Genetics
Pontecorvo Building
University of Glasgow
Glasgow G11 6NU, UK.
Phone: +44 (0)141 330 4616
FAX: +44 (0)141 330 5994
e-mail: j.a.t.dow@bio.gla.ac.uk
15) DOW, J.A.T. (1987). Insect midgut function. Advances insect Physiol. 19: 187-328
23) DOW, J.A.T., HARVEY, W.R. (1988). Role of midgut electrogenic K+ pump potential difference in regulating lumen K+ and pH in larval lepidoptera. J.exp.Biol. 140: 455-463
24) DOW, J.A.T., PEACOCK, J.M. (1989). Microelectrode evidence for the electrical isolation of goblet cavities of the middle midgut of Manduca sexta. J.exp.Biol. 143: 101-114
27) LACKIE, J.M.L., DOW, J.A.T. eds. (1989). The Dictionary of Cell Biology. London: Academic Press
30) DOW, J.A.T., O'DONNELL, M.J. (1990). Reversible alkalinization by Manduca sexta midgut. J.exp.Biol. 150: 247-256
41) DOW, J.A.T. (1992). pH gradients in lepidopteran midgut. J.exp. Biol. 172: 355-275
42)
DOW, J.A.T., GOODWIN, S.F., KAISER, K. (1992). Analysis of the gene encoding
a 16ÊkDa proteolipid subunit of the vacuolar H+-ATPase
from Manduca sexta midgut and tubules. Gene 122: 355-360.
46) KNOWLES, B.H. , DOW, J.A.T. (1993). The crystal d-endotoxins of Bacillus thuringiensis: models for their mechanism of action on the insect gut. Bioessays 15: 469-476.
48)
DOW, J.A.T., MADDRELL, S.H.P. (1993). Fluid secretion by the Malpighian
tubule of Drosophila melanogaster is stimulated by nitric oxide
and cyclic GMP. J. Physiol. 473: 233-233
50)
DOW, J.A.T., MADDRELL, S.H.P., SKAER, N. J. V., DAVIES, S.-A., KAISER,
K. (1994). A novel role for the NO/cGMP signalling pathway: the control
of fluid secretion in Drosophila. Amer. J. Physiol. 266:
R1716-R1719
51) DOW, J. A. T., MADDRELL, S. H. P., GOERTZ, A., SKAER, N. J.V., BROGAN, S., KAISER, K. (1994). The Malpighian tubules of Drosophila melanogaster: a novel phenotype for studies of fluid secretion and its control. J. exp. Biol. 197, 421- 428.
54) DOW, J.A.T. (1994). V-ATPases in insects. pp. 75-102 in NELSON, N. ed. 'Organellar Proton ATPases' R.G. Landes Company: Austin, Texas.
55)
DAVIES, S. A., DOW, J. A. T., HEUSMANN, G. R., MADDRELL, S. H. P., O'DONNELL,
M. J., TUBLITZ, N. J. (1994). CAP2b, a cardioactive peptide
of lepidopteran insect s, can also stimulate fluid production by Malpighian
tubules of Drosophila melanogaster through a mechanism involving
cGMP. J. Physiol. 482, P26-P26.
56) TUBLITZ, N. J., BATE, M., DAVIES, S. A., DOW, J. A. T., MADDRELL, S. H. P. (1994). A neuronal function for the midline mesodermal cells in Drosophila. In Society for Neuroscience 1994 Annual meeting (Miami Beach, Florida), Society for Neuroscience (Abstract).
58) SUMNER, J. P., DOW, J. A. T., EARLEY, F., KLEIN, U., JAEGER, D., WIECZOREK,
H. (1995). Regulation of plasma membrane H+ V-ATPase activity
by dissociation of peripheral subunits. Journal of Biological Chemistry
270, 5649-5653.
61) LACKIE, J.M.L., DOW, J.A.T. eds. (1995). The Dictionary of Cell Biology (Second edition). London: Academic Press
62)
DAVIES, S. A., HUESMANN, G. R., MADDRELL, S. H. P., O'DONNELL, M. J., DOW,
J. A. T., and TUBLITZ, N. J. (1995). CAP2b, a cardioacceleratory
peptide, is present in Drosophila and stimulates tubule fluid secretion
via cGMP. Am.J. Physiol. 269, R1321-R1326
63)
DOW, J.A.T., KELLY, D.C., DAVIES, S.A., MADDRELL, S.H.P., BROWN, D. (1995).
A member of the Major Intrinsic Protein family in Drosophila tubules.
J. Physiol. 489: 110P.
64)
GUO,Y., KAISER, K., WIECZOREK, H., DOW, J.A.T. (1995). vha14, the
Drosophila gene for a 14 kDa F-subunit of the vacuolar ATPase. Gene
172: 239-243
66) DOW, J. A. T. (1995). Cell biologists can surf, too! Trends in Cell Biology 5 (12): 474-6.
68) O'DONNELL, M.J., DOW, J.A.T., HUESMANN, G.R., TUBLITZ, N.J., MADDRELL,
S.H.P. (1996). Separate control of anion and cation transport in Malpighian
tubules of Drosophila melanogaster. J.exp.Biol. 199:
1163-1175
69) GUO, Y., WANG, Z., CARTER, A., KAISER, K. and DOW, J. A. T. (1996).
Characterisation of vha26, the Drosophila gene for a 26kDa
E-subunit of the vacuolar ATPase. Biochim. Biophys. Acta 1283:
4-9.
70) GUO, Y. GILLAN, A., TOROK, T., KISS, I., DOW, J.A.T., KAISER, K. (1996). Site-selected mutagenesis of the Drosophila second chromosome via plasmid rescue of lethal P-element insertions. Genome Research 6:972-979.
53) DAVIES, S. A., KELLY, D. C., GOODWIN, S. F., YANG, S., SOZEN, M. A.,
KAISER, K., and DOW, J. A. T. (1996). Analysis and inactivation of vha55,
the gene encoding the V-ATPase B subunit in Drosophila melanogaster
reveals a larval lethal phenotype. Journal of Biological Chemistry
271: 30677-30684.
71) DOW, J. A. T., DAVIES, S. A., GUO, Y., GRAHAM, S., FINBOW, M. E., KAISER,
K. (1997). Molecular genetic analysis of V-ATPase function in Drosophila
melanogaster. J. exp. Biol. 202: 237-245.
72) DOW, J. A. T. (1997). Internet resources for cell biologists. In: Cell Biology: a laboratory handbook (Second edition), vol. 3 (ed. J. E. Celis), pp. In press. San Diego: Academic Press.
73) ROSAY, P., DAVIES, S.A., SOZEN, M.A., DOW, J.A.T., KAISER, K. (1996). A cell-specific system for monitoring calcium in Drosophila using an aequorin expression system. Eur. J. Neurosci. in press (abstract).
59) SöZEN, M. A., ARMSTRONG, J. D., YANG, M.-Y., KAISER, K., DOW,
J. A. T. (1997). Functional compartments specified to single-cell resolution
in a Drosophila epithelium. Proc. Natl Acad. Sci. USA 94:
(in press)
74) DOW, J. A. T., DAVIES, S. A. AND SÖZEN, M. A. (1997). Fluid secretion by the Drosophila melanogaster Malpighian tubule. Amer. Zool. 38: (in press).
75) DAVIES, S.A., STEWART, E.J., HUESMANN, G.R., SKAER, N.J.V., MADDRELL, S.H.P., TUBLITZ, N.J., DOW, J.A.T. (1997). Neuropeptide stimulation of the nitric oxide signalling pathway in Drosophila melanogaster Malpighian tubules. Am. J. Physiol. (in press).