Ptf1a Directly Controls Expression of Immunoglobulin Superfamily Molecules Nephrin and Neph3 in the Developing Central Nervous System

Nishida, Keiya; Hoshino, Mikio; Kawaguchi, Yoshiya; Murakami, Fujio

doi:10.1074/jbc.m109.060657

Cited by 37 publications

(29 citation statements)

References 51 publications

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“…Because the Neph3 promoter is a direct target of Ptf1a, Gsx1 should be heterochronically expressed in the entire Ptf1a domain even at earlier stages such as E12.5 (ref. 34). Here, we equally divide the Ptf1a and Lhx1/5 + (c2) domains into three regions along the dorsoventral axis for the sake of convenience: ventral, intermediate and dorsal regions (green, yellow and red lines in Figs 1a–d, 4a–h and 5a,e,i,m).…”

Section: Resultsmentioning

confidence: 99%

Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum

et al. 2014

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In the cerebellum, all GABAergic neurons are generated from the Ptf1a-expressing ventricular zone (Ptf1a domain). However, the machinery to produce different types of GABAergic neurons remains elusive. Here we show temporal regulation of distinct GABAergic neuron progenitors in the cerebellum. Within the Ptf1a domain at early stages, we find two subpopulations; dorsally and ventrally located progenitors that express Olig2 and Gsx1, respectively. Lineage tracing reveals the former are exclusively Purkinje cell progenitors (PCPs) and the latter Pax2-positive interneuron progenitors (PIPs). As development proceeds, PCPs gradually become PIPs starting from ventral to dorsal. In gain- and loss-of-function mutants for Gsx1 and Olig1/2, we observe abnormal transitioning from PCPs to PIPs at inappropriate developmental stages. Our findings suggest that the temporal identity transition of cerebellar GABAergic neuron progenitors from PCPs to PIPs is negatively regulated by Olig2 and positively by Gsx1, and contributes to understanding temporal control of neuronal progenitor identities.

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Section: Resultsmentioning

confidence: 99%

Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum

et al. 2014

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“…4A). This region contains two consensus PTF1 motifs; both are required for reporter expression in vitro (35,36). At E12.5, the Kirrel2/Nphs1 enhancer faithfully recapitulates endogenous Ptf1a expression, as well as that of Kirrel2 and Nphs1 (35)(36)(37)(38)(39), in both dorsal neural tube and pancreas ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Program Specificity for Ptf1a in Pancreas versus Neural Tube Development Correlates with Distinct Collaborating Cofactors and Chromatin Accessibility

Meredith

Borromeo

Deering

et al. 2013

Molecular and Cellular Biology

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The lineage-specific basic helix-loop-helix transcription factor Ptf1a is a critical driver for development of both the pancreas and nervous system. How one transcription factor controls diverse programs of gene expression is a fundamental question in developmental biology. To uncover molecular strategies for the program-specific functions of Ptf1a, we identified bound genomic regions in vivo during development of both tissues. Most regions bound by Ptf1a are specific to each tissue, lie near genes needed for proper formation of each tissue, and coincide with regions of open chromatin. The specificity of Ptf1a binding is encoded in the DNA surrounding the Ptf1a-bound sites, because these regions are sufficient to direct tissue-restricted reporter expression in transgenic mice. Fox and Sox factors were identified as potential lineage-specific modifiers of Ptf1a binding, since binding motifs for these factors are enriched in Ptf1a-bound regions in pancreas and neural tube, respectively. Of the Fox factors expressed during pancreatic development, Foxa2 plays a major role. Indeed, Ptf1a and Foxa2 colocalize in embryonic pancreatic chromatin and can act synergistically in cell transfection assays. Together, these findings indicate that lineage-specific chromatin landscapes likely constrain the DNA binding of Ptf1a, and they identify Fox and Sox gene families as part of this process.

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“…This cooperation was further supported by the physical interaction of WT1 and NF-jB. This adds further evidence for common mechanisms in nephrin and Neph3 regulation since previous studies show that transcription factors Sp1 and Ptf1a are involved in both nephrin and Neph3 regulation in podocytes [8,16] and in developing central nervous system [6], respectively. Our results suggest that it is more likely that separate response element regions rather than one common promoter regulate nephrin and Neph3 genes.…”

Section: Discussionmentioning

confidence: 51%

“…Neph3, a member of Neph protein family (Neph1-3), is structurally related to nephrin and it also localizes at the SD [4,5]. Neph3 homodimerizes and heterodimerizes with nephrin and Neph1 suggesting that these molecules form a complex, which may be important for SD assembly [6,7].…”

Section: Introductionmentioning

confidence: 99%

Transcription of nephrin-Neph3 gene pair is synergistically activated by WT1 and NF- B and silenced by DNA methylation

Ristola

Arpiainen

Saleem

et al. 2011

Nephrology Dialysis Transplantation

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Background. Nephrin and Neph3 are homologous molecules expressed in the podocyte slit diaphragms that are essential for normal glomerular ultrafiltration. Nephrin and Neph3 genes form a bidirectional gene pair suggesting that they may share key features in their regulation. We investigated if nephrin and Neph3 genes have similar mechanisms in their transcriptional regulation focussing on transcription factor Wilms' tumour 1 (WT1) and nuclear factor-jB (NF-jB) and DNA methylation. Methods. Transcriptional regulation of nephrin and Neph3 by WT1 and NF-jB was analysed by overexpression studies, reporter gene assay and chromatin immunoprecipitation using A293 cells and cultured podocytes. The interaction between WT1 and NF-jB was studied by coimmunoprecipitation. The effect of NF-jB activator tumour necrosis factor-a (TNF-a) with or without NF-jB pathway inhibitor (BAY 11-7082) on nephrin and Neph3 messenger RNA (mRNA) expression and on cellular distribution of NF-jB was determined by quantitative polymerase chain reaction (PCR) and immunostaining, respectively. The role of DNA methylation in regulating nephrin and Neph3 genes was studied by demethylating agent (5-aza-2#-deoxycytidine) treatment and quantitative PCR. Results. WT1 and NF-jB interact with nephrin and Neph3 promoter and cooperatively regulate nephrin and Neph3. The cooperation was further supported by the physical interaction between WT1 and NF-jB. TNF-a increased nephrin and Neph3 mRNA expression and this effect was mediated by NF-jB. Furthermore, DNA methylation played a role in silencing nephrin and Neph3 expression in a cell-type and differentiation stage-dependent manner. Conclusion. These results provide novel insights into the transcriptional regulation of nephrin and Neph3 genes and indicate that nephrin and Neph3 share the same mechanisms in their regulation.

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Ptf1a Directly Controls Expression of Immunoglobulin Superfamily Molecules Nephrin and Neph3 in the Developing Central Nervous System

Cited by 37 publications

References 51 publications

Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum

Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum

Program Specificity for Ptf1a in Pancreas versus Neural Tube Development Correlates with Distinct Collaborating Cofactors and Chromatin Accessibility

Transcription of nephrin-Neph3 gene pair is synergistically activated by WT1 and NF- B and silenced by DNA methylation

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