title: Tbx18 is essential for normal development of vasculature network and glomerular mesangium in the mammalian kidney.
abstract: Tbx18 has been shown to be essential for ureteral development. However, it remains unclear whether it plays a direct role in kidney development. Here we addressed this by focusing on examining the pattern and contribution of Tbx18+ cells in the kidney and its role in kidney vascular development. Expression studies and genetic lineage tracing revealed that Tbx18 is expressed in renal capsule, vascular smooth muscle cells and pericytes and glomerular mesangial cells in the kidney and that Tbx18-expressing progenitors contribute to these cell types. Examination of Tbx18(-/-) kidneys revealed large reduction in vasculature density and dilation of glomerular capillary loops. While SMA+ cells were reduced in the mutant, PDGFRβ+ cells were seen in early capillary loop renal corpuscles in the mutant, but fewer than in the controls, and further development of the mesangium failed. Analysis of kidney explants cultured from E12.5 excluded the possibility that the defects observed in the mutant were caused by ureter obstruction. Reduced proliferation in glomerular tuft and increased apoptosis in perivascular mesenchyme were observed in Tbx18(-/-) kidneys. Thus, our analyses have identified a novel role of Tbx18 in kidney vasculature development.
authors.affiliation: Departments of Genetics and Genomic Sciences, New York, NY 10029, USA.
authors.forename: Jinshu
authors.initials: J
authors.lastname: Xu
authors.affiliation: Departments of Genetics and Genomic Sciences, New York, NY 10029, USA.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Nie
authors.affiliation: Developmental Biology and Regenerative Medicine, New York, NY 10029, USA.|Center for Molecular Cardiology, New York, NY 10029, USA.|Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Cai
authors.affiliation: Developmental Biology and Regenerative Medicine, New York, NY 10029, USA.|Center for Molecular Cardiology, New York, NY 10029, USA.|Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Chen-Leng
authors.initials: CL
authors.lastname: Cai
authors.affiliation: Departments of Genetics and Genomic Sciences, New York, NY 10029, USA.|Developmental Biology and Regenerative Medicine, New York, NY 10029, USA.
authors.forename: Pin-Xian
authors.initials: PX
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D005920:Glomerular Mesangium / Q000196:embryology*; D007668:Kidney / Q000098:blood supply* / Q000196:embryology*; D051379:Mice; D008822:Mice, Transgenic; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000502:physiology*; D013997:Time Factors
chemical_list: D020825:T-Box Domain Proteins; C420983:Tbx18 protein, mouse; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: Glomerular mesangium; Interstitium; Kidney; Perivascular mesenchyme; Stromal cell; Tbx18; Vasculogenesis
references.citation: Nephron Exp Nephrol. 2005;99(1):e1-8
references.pmid: 15637462
references.citation: Am J Physiol Renal Physiol. 2002 Oct;283(4):F799-809
references.pmid: 12217872
references.citation: Development. 1999 Dec;126(24):5771-83
references.pmid: 10572052
references.citation: J Clin Invest. 1997 Aug 15;100(4):786-94
references.pmid: 9259576
references.citation: Nat Genet. 2001 Jan;27(1):74-8
references.pmid: 11138002
references.citation: Kidney Int Suppl. 1998 Sep;67:S7-11
references.pmid: 9736245
references.citation: Nat Genet. 1999 Jan;21(1):70-1
references.pmid: 9916792
references.citation: Am J Pathol. 2010 Jan;176(1):85-97
references.pmid: 20008127
references.citation: J Cell Physiol. 2012 Mar;227(3):1257-68
references.pmid: 21830217
references.citation: Cell Tissue Res. 1994 Aug;277(2):247-57
references.pmid: 8082119
references.citation: Kidney Int. 2000 May;57(5):2167-8
references.pmid: 10792639
references.citation: Dev Genet. 1999;24(3-4):241-51
references.pmid: 10322632
references.citation: Development. 2010 Mar;137(5):755-65
references.pmid: 20110314
references.citation: Development. 2003 Jul;130(14):3085-94
references.pmid: 12783782
references.citation: J Biol Chem. 2008 Sep 12;283(37):25372-25380
references.pmid: 18644785
references.citation: Pediatr Nephrol. 1999 May;13(4):347-54
references.pmid: 10454789
references.citation: Dev Biol. 2013 Aug 1;380(1):25-36
references.pmid: 23685333
references.citation: J Cell Biol. 1986 Sep;103(3):1101-7
references.pmid: 2427526
references.citation: Genes Dev. 1996 Jun 15;10(12):1467-78
references.pmid: 8666231
references.citation: Development. 2005 Feb;132(3):529-39
references.pmid: 15634693
references.citation: Pediatr Nephrol. 1987 Jul;1(3):385-92
references.pmid: 3153305
references.citation: Development. 1998 Sep;125(17):3313-22
references.pmid: 9693135
references.citation: Am J Physiol. 1993 Jul;265(1 Pt 2):F151-6
references.pmid: 7688188
references.citation: Clin Exp Pharmacol Physiol. 2011 Jul;38(7):467-73
references.pmid: 21517936
references.citation: Eur Rev Med Pharmacol Sci. 1999 Jul-Aug;3(4):149-53
references.pmid: 11073120
references.citation: Nature. 2008 Jul 3;454(7200):104-8
references.pmid: 18480752
references.citation: Development. 1988 Mar;102(3):471-8
references.pmid: 2460305
references.citation: J Am Soc Nephrol. 2001 Mar;12(3):624-632
references.pmid: 11181813
references.citation: Anat Embryol (Berl). 1986;175(1):1-6
references.pmid: 3799983
references.citation: Science. 1997 Jul 11;277(5323):242-5
references.pmid: 9211853
references.citation: Development. 1999 Mar;126(6):1139-48
references.pmid: 10021334
references.citation: Microsc Res Tech. 1997 Nov 1;39(3):254-60
references.pmid: 9372498
references.citation: J Clin Invest. 2006 Mar;116(3):663-74
references.pmid: 16511601
references.citation: Annu Rev Cell Dev Biol. 2006;22:509-29
references.pmid: 16822174
references.citation: J Am Soc Nephrol. 2011 Dec;22(12):2156-65
references.pmid: 22052047
references.citation: Genes Dev. 2004 May 15;18(10):1209-21
references.pmid: 15155583