title: The bigger the better: determining nephron size in kidney.
abstract: The main functions of the kidney are to excrete metabolic waste products and actively reabsorb essential molecules such as amino acids, ions, glucose and water. In humans, a wide range of genetic disorders exist characterized by wasting of metabolically important compounds. At the cellular level, more than 20 highly specialized renal epithelial cell types located in different segments of the nephron contribute to the reabsorption process. In particular, proximal tubular cells play a crucial role and are uniquely adapted to maximize reabsorption efficiency. They accommodate high numbers of transporters and channels by increasing the apical surface area in contact with the primary filtrate by forming a brush border as well as undergoing hypertrophy and hyperplasia. This adaptation is evolutionarily conserved and is detected in the primitive pronephric kidney of fish and amphibians as well as the metanephric kidney of higher vertebrates. Surprisingly, signaling pathways regulating these three processes have remained largely unknown. Here we summarize recent studies that highlight the early phases of kidney development as a critical juncture in establishing proximal tubule size.
authors: Department Cellular and Molecular Medicine, Cleveland Clinic Foundation, Lerner Research Institute, 9500 Euclid Avenue/NC10, Cleveland, OH, 44195, USA, wesselo@ccf.org.
authors: Oliver
authors: O
authors: Wessely
authors: Débora M
authors: DM
authors: Cerqueira
authors: Uyen
authors: U
authors: Tran
authors: Vikash
authors: V
authors: Kumar
authors: Jessie M
authors: JM
authors: Hassey
authors: Daniel
authors: D
authors: Romaker
mesh_terms: D000818:Animals; D006801:Humans; D009399:Nephrons / Q000196:embryology* / Q000502:physiology*
references: Proc Natl Acad Sci U S A. 1988 Sep;85(18):6768-72
references: 3413124
references: Dev Biol. 2011 Dec 1;360(1):110-22
references: 21963425
references: Oncogene. 2005 Nov 14;24(50):7475-81
references: 16288294
references: Nat Med. 2007 Dec;13(12):1490-5
references: 17965720
references: Pediatr Res. 2008 Sep;64(3):240-5
references: 18535488
references: Nature. 2007 Jul 19;448(7151):366-9
references: 17597763
references: Kidney Int. 1991 Jul;40(1):13-20
references: 1921149
references: Hum Mol Genet. 2009 Nov 15;18(22):4428-41
references: 19692352
references: Cold Spring Harb Perspect Biol. 2011 Jan 01;3(1):a003228
references: 20980442
references: J Morphol. 2000 Sep;245(3):177-95
references: 10972968
references: Am J Physiol Renal Physiol. 2009 Sep;297(3):F809-15
references: 19535568
references: N Engl J Med. 1989 Mar 9;320(10):646-51
references: 2537465
references: Cell. 2012 Apr 13;149(2):274-93
references: 22500797
references: Kidney Int. 1993 Mar;43(3):610-4
references: 8455359
references: Compr Ther. 1991 May;17(5):8-17
references: 1879129
references: Kidney Int. 2002 Nov;62(5):1650-8
references: 12371965
references: PLoS One. 2012;7(7):e39992
references: 22815719
references: Klin Wochenschr. 1979 Oct 1;57(19):977-91
references: 392185
references: Lab Invest. 1991 Jun;64(6):777-84
references: 2046329
references: Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10830-5
references: 10485911
references: Dev Biol. 2007 Oct 15;310(2):379-87
references: 17826763
references: Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1631-6
references: 17251353
references: PLoS Genet. 2013 Mar;9(3):e1003380
references: 23555292
references: J Am Soc Nephrol. 2005 Feb;16(2):299-304
references: 15647335
references: Mol Cancer Res. 2012 Jul;10(7):859-80
references: 22638109
references: Proc Natl Acad Sci U S A. 2011 May 31;108(22):9226-31
references: 21576461
references: J Intern Med. 2007 Jan;261(1):17-31
references: 17222165
references: Endocr Rev. 2011 Jun;32(3):422-40
references: 21441345
references: Am J Physiol Cell Physiol. 2007 Feb;292(2):C807-13
references: 16987990
references: Acta Anat (Basel). 1972;82(3):305-6
references: 5048601
references: J Am Soc Nephrol. 2005 May;16(5):1384-91
references: 15788477
references: Pediatrics. 1965 Apr;35:601-19
references: 14269712
references: J Am Soc Nephrol. 2005 Feb;16(2):313-21
references: 15647339
references: J Cell Biol. 1968 Jun;37(3):703-15
references: 11905202
references: Curr Biol. 2012 May 8;22(9):R368-79
references: 22575479
references: Nat Rev Mol Cell Biol. 2006 Feb;7(2):85-96
references: 16493415
references: Clin Nephrol. 1984 Sep;22(3):149-57
references: 6488596
references: Nat Genet. 2012 Dec;44(12):1382-7
references: 23143599
references: Nat Genet. 2008 Oct;40(10):1163-5
references: 18724368
references: Pediatr Nephrol. 2005 Jul;20(7):854-7
references: 15856327
references: Genome Biol. 2008;9(5):R84
references: 18492243
references: Annu Rev Physiol. 1989;51:19-32
references: 2469382
references: Dev Biol. 2013 Apr 1;376(1):31-42
references: 23352791
references: Gastroenterology. 1978 Nov;75(5):783-90
references: 100367
references: Adv Nephrol Necker Hosp. 1972;2:35-60
references: 4219695
references: Am J Physiol Renal Physiol. 2009 Sep;297(3):F585-93
references: 19474189
references: Am J Hum Genet. 2001 Jan;68(1):264-8
references: 11090339
references: J Am Soc Nephrol. 2011 May;22(5):839-48
references: 21493775
references: Pediatr Endocrinol Rev. 2012 Nov;10(1):152-63
references: 23469392
references: Methods Mol Biol. 2012;886:121-32
references: 22639256
references: Dev Biol. 2004 Jul 15;271(2):322-38
references: 15223337
references: Development. 2003 Oct;130(19):4751-9
references: 12925600
references: Pediatr Nephrol. 2011 Sep;26(9):1435-43
references: 21336813
references: Acta Anat (Basel). 1976;95(1):8-33
references: 952201
references: Pediatr Nephrol. 2011 Sep;26(9):1545-51
references: 21499947
references: Am J Physiol Renal Physiol. 2008 Mar;294(3):F542-53
references: 18172001