EGFR/MAPK Signaling Regulates the Proliferation of Drosophila Renal and Nephric Stem Cells

Zhouhua Li; Sen Liu; Yu Cai

doi:10.1016/j.jgg.2014.11.007

Volume 42 Issue 1

Jan. 2015

Turn off MathJax

Article Contents

Article Navigation > Journal of Genetics and Genomics > 2015 > 42(1): 9-20

PDF( 3554 KB)

EGFR/MAPK Signaling Regulates the Proliferation of Drosophila Renal and Nephric Stem Cells

doi: 10.1016/j.jgg.2014.11.007

Zhouhua Li^{a, b},
Sen Liu^b,
Yu Cai^{b, c}

a
College of Life Sciences, Capital Normal University, Beijing 100048, China
b
Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Singapore
c
Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore

More Information

Corresponding author: E-mail address: zhli@cnu.edu.cn (Zhouhua Li); E-mail address: caiyu@tll.org.sg (Yu Cai)
Received Date: 2014-06-18
Accepted Date: 2014-11-29
Rev Recd Date: 2014-11-26

Available Online: 2014-12-09

Publish Date: 2015-01-20

Abstract

Abstract

Tissue homeostasis, accomplished through the self-renewal and differentiation of resident stem cells, is critical for the maintenance of adult tissues throughout an animal's lifetime. Adult Drosophila Malpighian tubules (MTs or fly kidney) are maintained by renal and nephric stem cells (RNSCs) via self-renewing divisions, however, it is unclear how RNSC proliferation and differentiation are regulated. Here we show that EGFR/MAPK signaling is dispensable for RNSC maintenance, but required for RNSC proliferation in vivo. Inactivation of the EGFR/MAPK pathway blocks or greatly retards RNSC cell cycle progression; conversely, over-activation of EGFR/MAPK signaling results in RNSC over-proliferation and disrupts the normal differentiation of renablasts (RBs), the immediate daughters of RNSC divisions. Our data further suggest that EGFR/MAPK signaling functions independently of JAK/STAT signaling and that dMyc and CycE partially mediate EGFR/MAPK signaling in MTs. Together, our data suggest a principal role of EGFR/MAPK signaling in regulating RNSC proliferation, which may provide important clues for understanding mammalian kidney repair and regeneration following injury.
- Renal and nephric stem cells,
- EGFR/MAPK signaling

FullText(HTML)

References(49)

References

[1]	Aguirre, A., Rubio, M.E., Gallo, V. Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal Nature, 467 (2010),pp. 323-327
[2]	Ainsworth, C., Wan, S., Skaer, H. Philos. Trans. R. Soc. Lond. B Biol. Sci., 355 (2000),pp. 931-937
[3]	Anglani, F., Ceol, M., Mezzabotta, F. et al. The renal stem cell system in kidney repair and regeneration Front. Biosci., 13 (2008),pp. 6395-6405
[4]	Biteau, B., Jasper, H. Development, 138 (2011),pp. 1045-1055
[5]	Brand, A.H., Perrimon, N. Genes Dev., 8 (1994),pp. 629-639
[6]	Buchon, N., Broderick, N.A., Kuraishi, T. et al. BMC Biol., 8 (2010),p. 152
[7]	Chao, J.L., Tsai, Y.C., Chiu, S.J. et al. Development, 131 (2004),pp. 3839-3847
[8]	de Nooij, J.C., Graber, K.H., Hariharan, I.K. Expression of the cyclin-dependent kinase inhibitor Dacapo is regulated by cyclin E Mech. Dev., 97 (2000),pp. 73-83
[9]	Denholm, B., Sudarsan, V., Pasalodos-Sanchez, S. et al. Curr. Biol., 13 (2003),pp. 1052-1057
[10]	Dow, J.A., Davies, S.A. The Malpighian tubule: rapid insights from post-genomic biology J. Insect Physiol., 52 (2006),pp. 365-378
[11]	Duchek, P., Rorth, P. Science, 291 (2001),pp. 131-133
[12]	Elger, M., Hentschel, H., Litteral, J. et al. Nephrogenesis is induced by partial nephrectomy in the elasmobranch Leucoraja erinacea J. Am. Soc. Nephrol., 14 (2003),pp. 1506-1518
[13]	Gabay, L., Seger, R., Shilo, B.Z. Science, 277 (1997),pp. 1103-1106
[14]	Ghiglione, C., , Amundadottir, L.T., Boswell, R.E. et al. Cell, 96 (1999),pp. 847-856
[15]	Gupta, S., Rosenberg, M.E. Do stem cells exist in the adult kidney? Am. J. Nephrol., 28 (2008),pp. 607-613
[16]	Haller, H., de Groot, K., Bahlmann, F. et al. Stem cells and progenitor cells in renal disease Kidney Int., 68 (2005),pp. 1932-1936
[17]	Holbro, T., Hynes, N.E. ErbB receptors: directing key signaling networks throughout life Annu. Rev. Pharmacol. Toxicol., 44 (2004),pp. 195-217
[18]	Ito, K., Awano, W., Suzuki, K. et al. Development, 124 (1997),pp. 761-771
[19]	Jekely, G., Rorth, P. EMBO Rep., 4 (2003),pp. 1163-1168
[20]	Jiang, H., Grenley, M.O., Bravo, M.J. et al. Cell Stem Cell, 8 (2010),pp. 84-95
[21]	Jung, A.C., Denholm, B., Skaer, H. et al. J. Am. Soc. Nephrol., 16 (2005),pp. 322-328
[22]	Klaes, A., Menne, T., Stollewerk, A. et al. Cell, 78 (1994),pp. 149-160
[23]	Lane, M.E., Sauer, K., Wallace, K. et al. Cell, 87 (1996),pp. 1225-1235
[24]	Lee, C.Y., Andersen, R.O., Cabernard, C. et al. Genes Dev., 20 (2006),pp. 3464-3474
[25]	Lee, T., Luo, L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis Neuron, 22 (1999),pp. 451-461
[26]	Li, Z., Liu, S., Cai, Y. J. Genet. Genomics, 41 (2014),pp. 649-652
[27]	Li, Z., Wang, L., Hays, T.S. et al. Dynein-mediated apical localization of crumbs transcripts is required for Crumbs activity in epithelial polarity J. Cell Biol., 180 (2008),pp. 31-38
[28]	Liu, M., Lim, T.M., Cai, Y. Sci. Signal., 3 (2010),p. ra57
[29]	Micchelli, C.A., Perrimon, N. Nature, 439 (2006),pp. 475-479
[30]	Moberg, K.H., Mukherjee, A., Veraksa, A. et al. Curr. Biol., 14 (2004),pp. 965-974
[31]	Morrison, S.J., Spradling, A.C. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life Cell, 132 (2008),pp. 598-611
[32]	Ohlstein, B., Spradling, A. Nature, 439 (2006),pp. 470-474
[33]	Ohlstein, B., Spradling, A. Science, 315 (2007),pp. 988-992
[34]	Pai, L.M., Barcelo, G., Schupbach, T. Cell, 103 (2000),pp. 51-61
[35]	Prober, D.A., Edgar, B.A. Cell, 100 (2000),pp. 435-446
[36]	Prober, D.A., Edgar, B.A. Genes Dev., 16 (2002),pp. 2286-2299
[37]	Pugacheva, O.M., Mamon, L.A. Ontogenez, 34 (2003),pp. 325-341
[38]	Queenan, A.M., Ghabrial, A., Schupbach, T. Development, 124 (1997),pp. 3871-3880
[39]	Repasky, G.A., Chenette, E.J., Der, C.J. Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis? Trends Cell Biol., 14 (2004),pp. 639-647
[40]	Richardson, H., O'Keefe, L.V., Marty, T. et al. Development, 121 (1995),pp. 3371-3379
[41]	Riggleman, B., Schedl, P., Wieschaus, E. Cell, 63 (1990),pp. 549-560
[42]	Shilo, B.Z. Exp. Cell Res., 284 (2003),pp. 140-149
[43]	Shilo, B.Z. Regulating the dynamics of EGF receptor signaling in space and time Development, 132 (2005),pp. 4017-4027
[44]	Singh, S.R., Hou, S.X. J. Exp. Biol., 212 (2009),pp. 413-423
[45]	Singh, S.R., Liu, W., Hou, S.X. Cell Stem Cell, 1 (2007),pp. 191-203
[46]	Sozen, M.A., Armstrong, J.D., Yang, M. et al. Proc. Natl. Acad. Sci. USA, 94 (1997),pp. 5207-5212
[47]	Vaidya, V.S., Ferguson, M.A., Bonventre, J.V. Biomarkers of acute kidney injury Ann. Rev. Pharmacol. Toxicol., 48 (2008),pp. 463-493
[48]	Xu, N., Wang, S.Q., Tan, D. et al. Dev. Biol., 354 (2011),pp. 31-43
[49]	Yokoo, T., Fukui, A., Matsumoto, K. et al. Stem cells and kidney organogenesis Front. Biosci., 13 (2008),pp. 2814-2832