Crucial roles of Brn1 in distal tubule formation and function in mouse kidney

Nakai, Shigeyasu; Sugitani, Yoshinobu; Sato, Hiroshi; Ito, Sadayoshi; Miura, Yukio; Ogawa, Michio; Nishi, Miyuki; Jishage, Kou Ichi; Minowa, Osamu; Noda, Tetsuo

doi:10.1242/dev.00666

Cited by 141 publications

(145 citation statements)

References 23 publications

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“…Studies of several signaling pathways, as well as transcription factors, have revealed genes involved in the patterning the nephron including Fgf8 (Grieshammer et al, 2005), Pou3f3 (Nakai et al, 2003),Sprouty (Basson et al, 2005;Basson et al, 2006), Notch/presenillins (Cheng et al, 2007;Cheng et al, 2003;McCright et al, 2002), and Lhx1 (Kobayashi et al, 2005). In particular, genetic studies have shown several members of the Wnt family of lipidmodified secreted glycoproteins have important roles in the initiation and maintenance of nephron formation and branching morphogenesis Kispert et al, 1998;Majumdar et al, 2003;Stark et al, 1994).…”

Section: Screen For Genes In Nephron Formationmentioning

confidence: 99%

“…Some genes failed to meet the statistical cutoff though they are expressed in E14.5 kidney. These included Fgf8 (Grieshammer et al, 2005), ret (Pachnis et al, 1993;Schuchardt et al, 1994), Pou3f3 (Nakai et al, 2003), Wnt7b (Kispert et al, 1996;Patterson et al, 2001), Ihh (Valentini et al, 1997), and Shh (Yu et al, 2002). Overall, the wildtype profiles had 6824 Present calls (54.9%) and the Wnt4 mutant profiles had 6628 Present calls (53.4%).…”

Section: Transcriptional Profiling Of Wnt4 Mutant Kidneysmentioning

confidence: 99%

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Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed during nephron formation

Valerius

McMahon

2008

Gene Expression Patterns

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The mature nephron forms from a simple epithelial vesicle into an elaborate structure with distinct regions of specialized physiological function. The molecular components driving the process of nephron development are not well understood. To identify genes that may be informative in this process we conducted a transcriptional profiling screen using Wnt4 mutant kidneys. In Wnt4 −/− homozygous mice, condensates and pretubular aggregates are induced, however, epithelial renal vesicles fail to form and subsequent tubulogenesis is blocked. A transcriptional profile comparison between wildtype and Wnt4−/− mutant kidneys at E14.5 was performed using Affymetrix oligonucleotide microarrays to identify nephron-expressed genes. This approach identified 236 genes with expression levels >1.8 fold higher in wildtype versus mutant kidneys, amongst these were a number of known nephron component markers confirming the validity of the screen. These results were further detailed by wholemount in situ hybridization (WISH) of E15.5 urogenital systems (UGS). We annotated the spatial expression pattern of these genes into eight categories of expression. Genes expressed in renal vesicle and their derivatives, structures absent in the mutant, accounted for the largest number of the observed expression patterns. A number of additional genes in areas not directly overlapping the Wnt4 expression domain were also identified including the cap mesenchyme, the collecting duct, and the cortical interstitium. This study provides a useful compendium of molecular markers for the study of nephrogenesis.

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Section: Screen For Genes In Nephron Formationmentioning

confidence: 99%

Section: Transcriptional Profiling Of Wnt4 Mutant Kidneysmentioning

confidence: 99%

Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed during nephron formation

Valerius

McMahon

2008

Gene Expression Patterns

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“…Far less is known how the more distal nephron segments are specified. Mouse embryos that lack Brn1 (Pou3f3), a POU domain transcription factor, initiate nephrogenesis but form truncated nephrons that lack the loop of Henle and distal tubules (Nakai et al 2003). Whether Brn1 is sufficient to specify these nephron segments is not known.…”

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confidence: 99%

The prepattern transcription factor Irx3 directs nephron segment identity

Reggiani

Raciti²,

Airik³

et al. 2007

Genes Dev.

105

169

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The nephron, the basic structural and functional unit of the vertebrate kidney, is organized into discrete segments, which are composed of distinct renal epithelial cell types. Each cell type carries out highly specific physiological functions to regulate fluid balance, osmolarity, and metabolic waste excretion. To date, the genetic basis of regionalization of the nephron has remained largely unknown.

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“…DLL1 contributes via NOTCH2 in the specification of proximal tubule fate (12,35). Under the control of transcription factors BRN1 and Iroquois-class homeodomain proteins IRX 1-3, distal segments further extend and differentiate toward the distal tubule and Henle's loop (46,49,76) (Fig. 1).…”

Section: Transcriptional Network In Nephron Patterningmentioning

confidence: 99%

“…1). Brn1Ϫ/Ϫ mutant mice show disrupted development of Henle's loop and formation of distal convoluted tubules (46). In X. laevis, a subset of Irx transcription factors (Irx1, Irx2, and Irx3) are specifically expressed in a medial zone of the developing pronephric anlagen, which will give rise to the intermediate tubule.…”

Section: Transcriptional Network In Nephron Patterningmentioning

confidence: 99%

Transcriptional control of terminal nephron differentiation

El‐Dahr

Aboudehen

Saifudeen

2008

American Journal of Physiology-Renal Physiology

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entiation of epithelial cells into more specialized cell types is a critical step in organogenesis. Throughout the process of terminal differentiation, epithelial progenitors acquire or upregulate expression of renal function genes and cease to proliferate, while expression of embryonic genes is repressed. This exquisite coordination of gene expression is accomplished by signaling networks and transcription factors which couple the external environment with the new functional demands of the cell. While there has been much progress in understanding the early steps involved in renal epithelial cell differentiation, a major gap remains in our knowledge of the factors that control the steps of terminal differentiation. A number of signaling molecules and transcription factors have been recently implicated in determining segmental nephron identity and functional differentiation. While some of these factors (the p53 gene family, hepatocyte nuclear factor-1␤) promote the terminal epithelial differentiation fate, others (Notch, Brn-1, IRX, KLF4, and Foxi1) tend to regulate differentiation of specific nephron segments and individual cell types. This review summarizes current knowledge related to these transcription factors and discusses how diverse cellular signals are integrated to generate a transcriptional output during the process of terminal differentiation. Since these transcriptional processes are accompanied by profound changes in nuclear chromatin structure involving the genes responsible for creating and maintaining the differentiated cell phenotype, future studies should focus on identifying the nature of these epigenetic events and factors, how they are regulated temporally and spatially, and the chromatin environment they eventually reside in. transcription factors; kidney development; p53; gene expression TERMINAL DIFFERENTIATION IS a key biological process characterized by cell cycle arrest and acquisition of specialized functions by each cell type. The genetic programs that couple cellular growth to functional differentiation are a subject of intense investigation (78). There is increasing appreciation that although formation of adequate numbers of nephrons (i.e., renal mass) is critical for achieving optimal renal function capacity, the signals that determine how, when, and which renal epithelial cells should acquire a given functional phenotype are equally essential. Aberrant terminal differentiation is a hallmark of dysplasia, cyst formation, and cancer, and therapeutic interventions to promote differentiation and cell cycle arrest [e.g., EGF receptor (EGFR) antagonists and histone deacetylase inhibitors] are effective measures in some models of polycystic kidney disease and cancer (17,26,72,73). Therefore, identification of factors that couple cell cycle arrest with functional differentiation is of great clinical importance. Termination of Nephrogenesis and Differentiation are Dynamic and Coordinated ProcessesThe metanephric kidney is derived from the intermediate mesoderm at embryonic (E) day 10.5 (E...

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Crucial roles of Brn1 in distal tubule formation and function in mouse kidney

Cited by 141 publications

References 23 publications

Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed during nephron formation

Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed during nephron formation

The prepattern transcription factor Irx3 directs nephron segment identity

Transcriptional control of terminal nephron differentiation

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