Math6 expression during kidney development and altered expression in a mouse model of glomerulosclerosis.
Math6 is a tissue-restricted member of the Atonal family of basic helix-loop-helix (bHLH) transcription factors and has been implicated in specification and differentiation of cell lineages in the brain. We identify here Math6 as a podocyte-expressed bHLH protein that was down-regulated in human immunodeficiency virus-associated nephropathy (HIVAN); a collapsing glomerulopathy characterized by podocyte dedifferentiation. Early in metanephric development, Math6 was expressed in metanephric mesenchyme but not ureteric bud-derived cells, with overall Math6 expression most abundant in the nephrogenic zone, including developing glomeruli. In adult kidney, Math6 expression was restricted to podocytes. In adult podocyte cell lines and kidneys from the transgenic mouse model of HIVAN, Math6 podocyte expression was reduced concurrent with previously reported reductions in Nephrin and Synaptopodin expression, suggesting a correlation between the loss of Math6 expression and typical podocyte terminal differentiation markers. These studies suggest that Math6 may participate in kidney development and may be a permissive factor for podocyte differentiation.
Ross
Michael D
MD
Department of Medicine and Rammelkamp Center for Education and Research, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Martinka
Scott
S
Mukherjee
Amitava
A
Sedor
John R
JR
Vinson
Charles
C
Bruggeman
Leslie A
LA
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000235:genetics; D007668:Kidney / Q000166:cytology / Q000196:embryology*; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D038081:Organogenesis; D050199:Podocytes / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D012333:RNA, Messenger; C449163:Atoh8 protein, mouse