Our research aims to understand the processes that ‘make and shape’ organs during animal development.
The internal organs of our bodies start out as small populations of non-specialised cells that transform into mature organs with defined sizes, intricate shapes and specific functions.
We study these processes using the simple excretory system of the fruit fly (Drosophila) as a model because it is easy to manipulate experimentally and genetically, but shares many features with more complex organs such as the vertebrate kidney.
By using a combination of genetic, genomic, cell, and physiological techniques we are exploring the processes that underpin development of the fly excretory system.
We anticipate our studies will provide fundamental insights into organogenesis more widely.
Our current research focuses on two different parts of the excretory system: renal (or Malpighian) tubules and nephrocytes.
We are using the Malpighian tubule to address how organ shape is sculpted during development, how cells with specialised activities arise during organ maturation, and how these two properties integrate to produce the defined physiological activities that characterise the mature organ.
Nephrocytes are specialized cells that filter the blood; they share remarkable similarities to the blood filtration cell of the vertebrate kidney - the podocyte.
By studying the nephrocyte our goal is understand the role of genes known to be required in human kidney (and in kidney diseases) but whose precise activities are currently obscure.
Saxena, A.*, Denholm, B.*, Bunt, S., Bischoff, M., VijayRaghavan, K. and Skaer, H. (2014) Epidermal Growth Factor Signalling Controls Myosin II Planar Polarity to Orchestrate Convergent Extension Movements during Drosophila Tubulogenesis. PLoS Biol 12(12):e1002013
King, B. and Denholm, B.¶ (2014) Malpighian tubule development in the red flour beetle (Tribolium castaneum). Arthropod Structure & Development 43(6):605-13
Denholm, B.*¶, Hu, N*., Fauquier, T., Caubit, X., Fasano, L., and Skaer, H¶,. (2013) The teashirt/tiptop genes regulate cell differentiation and renal physiology in Drosophila. Development 140(5): 1100-1110
Denholm, B. ¶ (2013) Shaping up for action: the path to physiological maturation in the renal tubules of Drosophila. Organogenesis 9(1)
Pulver, S.*, Cognigni P.*, Denholm, B.*, Fabre, C.*, Gu, W.*, Linneweber, G.*, Prieto-Godino, L.*, Urbancic, V.*, Zwart, M.*, and Miguel-Aliaga, I*. (2011) Why flies? Inexpensive public engagement exercises to explain the value of basic biomedical research on Drosophila meleanogaster. Advances in Physiology education 35: 384-392
Bunt, S.*, Denholm, B.* and Skaer, H. (2011) Characterization of the Drosophila procollagen lysyl hydroxylase dPlod. Gene Expression Patterns 11(1-2): 72-8
Weavers, H, Prieto-Sánchez, S, Grawe, F, Garcia-López, A, Artero, R, Wilsch-Bräuninger, M, Ruiz-Gómez, M, Skaer, H, Denholm, B. ¶ (2009). The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm. Nature 457: 322-326
Denholm, B., and Skaer, H. (2009) Bringing together components of the fly renal system. Current Opinions in Genetics and Development 19(5): 526-32
Simões S, Denholm B., Sotillos S, Martin P, Skaer H, Castelli-Gair Hombría J, and Jacinto A. (2006). Compartmentalization of Rho regulators directs cell invagination during tissue morphogenesis. Development 133(21): 4257-67
Denholm B., Brown S, Ray RP, Ruiz-Gomez M, Skaer H, Hombria JC. (2005).crossveinless-c is a RhoGAP required for actin reorganisation during morphogenesis. Development 132(10):2389-400
Jung AC, Denholm B., Skaer H, Affolter M. (2005). Renal tubule development in Drosophila: a closer look at the cellular level. J Am Soc Nephrol. 16(2):322-8
Denholm, B. and Skaer, H. (2005). Development of Malpighian tubules in insects. In Comprehensive Molecular Insect Science, Vol 2 (ed. L.I. Gilbert, S. Gill and K. Iatrou), pp. 291-314. Oxford, UK: Elsevier.
Denholm B., Sudarsan V, Pasalodos-Sanchez S, Artero R, Lawrence P, Maddrell S, Baylies M, Skaer H. (2003). Dual origin of the renal tubules in Drosophila: mesodermal cells integrate and polarize to establish secretory function. Current Biology. 13(12):1052-7
Denholm B., Skaer H. (2003). Tubulogenesis: a role for the apical extracellular matrix? Current Biology. 13(23):R909-11
* equal contribution, ¶ corresponding author