Aditya Saxena

Research area – Development and Organogenesis

Organogenesis describes a series of organized processes that transform amorphous cell masses into complete organs in the developing embryo. In the lab we’re interested in these processes, how they are controlled and how they are integrated with one another. Our experimental model of choice is the fly excretory system. This system consists of two main components: renal (Malpighian) tubules and nephrocytes, that together regulate haemolymph (insect blood) composition by controlling salt and water balance, and by removing from it toxic and unwanted materials. This is a simple organ system benefiting from ease of experimental manipulation and tractable genetics afforded by the fly, but also one that 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 to gain fundamental insights into organogenesis.

We have recently shown that fly nephrocytes bear striking resemblance to the podocyte of the vertebrate kidney (see figure below). In particular, nephrocytes make a filtration barrier that is structurally, molecularly and functionally highly similar to the podocyte slit diaphragm, the main size-selective barrier in the kidney as blood is ultrafiltered to make urine. This work, and previous studies in other invertebrates, suggests that invertebrate excretory systems may be more related to the vertebrate kidney than previously thought. We are studying the development, cell biology and physiology of the nephrocyte to learn more about this important part of the insect excretory system, but in addition, we hope that it will prove to be a useful model to study podocyte biology and podocyte-associated diseases.

Recent publications

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

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, R.P., Ruiz-Gomez, M., Skaer, H., Hombria, J.C. (2005) crossveinless-c is a RhoGAP required for actin reorganisation during morphogenesis. Development 132(10):2389-400

Jung, A.C., Denholm, B., Skaer, H., Affolter, M. (2005) Renal tubule development in Drosophila: a closer look at the cellular level. Journal of the American Society of Nephrology. 16(2):322-8

Denholm, B. and Skaer, H. (2004) 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. and Skaer, H. (2003) Tubulogenesis: a role for the apical extracellular matrix? Current Biology 13(23):R909-11.

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.