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Research
General Information
ZIRC
ZFIN ID: ZDB-PERS-000913-13
Majumdar, Arindam
Email: arindam.majumdar@igp.uu.se
URL:
Affiliation: Arindam Majumdar Lab
Address: Department of Immunology, Genetics, and Pathology Rudbecklaboratoriet Uppsala University Dag Hammarskjölds väg 20 Uppsala , 751 85 Sweden
Country: Sweden
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BIOGRAPHY AND RESEARCH INTERESTS
Our research group is interested in the developmental signals that control growth and differentiation during vertebrate kidney organogenesis. Because the nephron is the functional unit of the kidney and the pathophysiological site of human kidney diseases, including those affecting the glomerulus, we have concentrated our research efforts on understanding the molecular/genetic regulation of nephron formation. Topics of investigation include nephron segmentation, tubulogenesis, and glomerular morphogenesis.

Our lab is using the zebrafish embryonic kidney or pronephros as a model sytem for investigating kidney organogenesis due to its several experimental advantages. The pronephros, made of two unit nephrons with glomerulus, tubule, and duct segments, shares structural features with nephrons from higher vertebrates yet is anatomically much simpler. Zebrafish pronephric development follows developmental stages common to nephrogenesis in mammals but is complete by 48 hours post fertilization (hpf), much faster than in mouse. Embryonic development occurs ex utero offering the potential for experimental manipulation such as cell labeling and cell transplantation. In addition, zebrafish embryos are transparent allowing the direct visualization of pronephric organogenesis in the living embryo and in transgenic GFP expressing reporter strains. Finally, renal physiological function can be assayed by the uptake of injected, fluorescently labeled small molecules such as dextran.

The zebrafish mutant no isthmus (noi) contains a mutation in the transcription factor Pax2.1 and is associated with pleiotrophic defects in midbrain/hindbrain patterning, retinal axon pathfinding, and pronephric development. During pronephric organogenesis, pronephric tubules do not form in noi mutants (Development, 127, pp. 2089-98, 2000). The developmental basis lies in the expansion of glomerular specific gene expression domains within kidney tubule progenitor cells suggesting that the Pax2.1 transcription factor is important in controlling nephron patterning events. We are using the noi Pax2.1 mutant as an entrance point into investigating the genetic pathways regulating nephron segmentation and tubular differentiation. Approaches involve genetic screens, antisense morpholino technology, microarrays, and transgenesis.

In collaboration with Karl Tryggvason’s group in the Division of Matrix Biology, we are also using the zebrafish to study the function of several glomerular associated genes. These include genes expressed uniquely in the glomerular podocytes, mesangial cells, and capillary endothelial cells. Our goal is to identify central regulators of glomerular morphogenesis and physiological function.


PUBLICATIONS
Hildebrand, S., Hultin, S., Subramani, A., Petropoulos, S., Zhang, Y., Cao, X., Mpindi, J., Kalloniemi, O., Johansson, S., Majumdar, A., Lanner, F., Holmgren, L. (2017) The E-cadherin/AmotL2 complex organizes actin filaments required for epithelial hexagonal packing and blastocyst hatching. Scientific Reports. 7:9540
Hultin, S., Subramani, A., Hildebrand, S., Zheng, Y., Majumdar, A., Holmgren, L. (2017) AmotL2 integrates polarity and junctional cues to modulate cell shape. Scientific Reports. 7:7548
Abu-Siniyeh, A., Owen, D.M., Benzing, C., Rinkwitz, S., Becker, T.S., Majumdar, A., Gaus, K. (2016) The aPKC/Par3/Par6 polarity complex and membrane order are functionally inter-dependent in epithelia during vertebrate organogenesis. Traffic (Copenhagen, Denmark). 17(1):66-79
Ebarasi, L., Ashraf, S., Bierzynska, A., Gee, H.Y., McCarthy, H.J., Lovric, S., Sadowski, C.E., Pabst, W., Vega-Warner, V., Fang, H., Koziell, A., Simpson, M.A., Dursun, I., Serdaroglu, E., Levy, S., Saleem, M.A., Hildebrandt, F., Majumdar, A. (2015) Defects of CRB2 Cause Steroid-Resistant Nephrotic Syndrome. American journal of human genetics. 96(1):153-61
Hultin, S., Zheng, Y., Mojallal, M., Vertuani, S., Gentili, C., Balland, M., Milloud, R., Belting, H.G., Affolter, M., Helker, C.S., Adams, R.H., Herzog, W., Uhlen, P., Majumdar, A., Holmgren, L. (2014) AmotL2 links VE-cadherin to contractile actin fibres necessary for aortic lumen expansion. Nature communications. 5:3743
Hayashi, M., Majumdar, A., Li, X., Adler, J., Sun, Z., Vertuani, S., Hellberg, C., Mellberg, S., Koch, S., Dimberg, A., Young Koh, G., Dejana, E., Belting, H.G., Affolter, M., Thurston, G., Holmgren, L., Vestweber, D., and Claesson-Welsh, L. (2013) VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation. Nature communications. 4:1672
Owen, D.M., Magenau, A., Majumdar, A., and Gaus, K. (2010) Imaging membrane lipid order in whole, living vertebrate organisms. Biophysical journal. 99(1):L7-L9
Ebarasi, L., He, L., Hultenby, K., Takemoto, M., Betsholtz, C., Tryggvason, K., and Majumdar, A. (2009) A reverse genetic screen in the zebrafish identifies crb2b as a regulator of the glomerular filtration barrier. Developmental Biology. 334(1):1-9
Zheng, Y., Vertuani, S., Nyström, S., Audebert, S., Meijer, I., Tegnebratt, T., Borg, J.P., Uhlén, P., Majumdar, A., and Holmgren, L. (2009) Angiomotin-Like Protein 1 Controls Endothelial Polarity and Junction Stability During Sprouting Angiogenesis. Circulation research. 105(3):260-270
Sekine, Y., Nishibori, Y., Akimoto, Y., Kudo, A., Ito, N., Fukuhara, D., Kurayama, R., Higashihara, E., Babu, E., Kanai, Y., Asanuma, K., Nagata, M., Majumdar, A., Tryggvason, K., and Yan, K. (2009) Amino Acid Transporter LAT3 Is Required for Podocyte Development and Function. Journal of the American Society of Nephrology : JASN. 20(7):1586-1596
Vasilyev, A., Liu, Y., Mudumana, S., Mangos, S., Lam, P.Y., Majumdar, A., Zhao, J., Poon, K.L., Kondrychyn, I., Korzh, V., and Drummond, I.A. (2009) Collective Cell Migration Drives Morphogenesis of the Kidney Nephron. PLoS Biology. 7(1):e9
Ernkvist, M., Luna Persson, N., Audebert, S., Lecine, P., Sinha, I., Liu, M., Schlueter, M., Horowitz, A., Aase, K., Weide, T., Borg, J.P., Majumdar, A., and Holmgren, L. (2009) The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells. Blood. 113(1):244-253
Raschperger, E., Neve, E.P., Wernerson, A., Hultenby, K., Pettersson, R.F., and Majumdar, A. (2008) The coxsackie and adenovirus receptor (CAR) is required for renal epithelial differentiation within the zebrafish pronephros. Developmental Biology. 313(1):455-464
Aase, K., Ernkvist, M., Ebarasi, L., Jakobsson, L., Majumdar, A., Yi, C., Birot, O., Ming, Y., Kvanta, A., Edholm, D., Aspenström, P., Kissil, J., Claesson-Welsh, L., Shimono, A., and Holmgren, L. (2007) Angiomotin regulates endothelial cell migration during embryonic angiogenesis. Genes & Development. 21(16):2055-2068
Majumdar, A. and Drummond, I.A. (2000) The zebrafish floating head mutant demonstrates podocytes play an important role in directing glomerular differentiation. Developmental Biology. 222(1):147-157
Majumdar, A., Lun, K., Brand, M., and Drummond, I.A. (2000) Zebrafish no isthmus reveals a role for pax2.1 in tubule differentiation and patterning events in the pronephric primordia. Development (Cambridge, England). 127(10):2089-2098
Liu, A., Majumdar, A., Schauerte, H.E., Haffter, P., and Drummond, I.A. (2000) Zebrafish wnt4b expression in the floor plate is altered in sonic hedgehog and gli-2 mutants. Mechanisms of Development. 91(1-2):409-413
Majumdar, A. and Drummond, I.A. (1999) Podocyte differentiation in the absence of endothelial cells as revealed in the zebrafish avascular mutant, cloche. Developmental genetics. 24(3-4):220-229
Drummond, I.A., Majumdar, A., Hentschel, H., Elger, M., Solnica-Krezel, L., Schier, A.F., Neuhauss, S.C., Stemple, D.L., Zwartkruis, F., Rangini, Z., Driever, W., and Fishman, M.C. (1998) Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function. Development (Cambridge, England). 125:4655-4667

NON-ZEBRAFISH PUBLICATIONS
Drummond, I.A. and Majumdar, A. (2003) Pronephric glomus and vasculature. In The Kidney: From Normal Development to Congenital Disease, P. Vize, A. Woolf, and J. Bard, eds., Amsterdam, Boston: Academic Press.

Majumdar, A., Vainio, S., Kispert, A., McMahon, J.A., and McMahon, A.P. (2003) Wnt11 and Ret/GDNF pathways cooperate in regulating ureteric branching during metanephric kidney development. Development 130(14):3175-3185.