Sall1, Sall2, and Sall4 Are Required for Neural Tube Closure in Mice

Böhm, Johann; Buck, Anna; Borozdin, Wiktor; Mannan, Ashraf U.; Matysiak-Scholze, Uta; Adham, Ibrahim M.; Schulz‐Schaeffer, Walter; Floss, Thomas; Wurst, Wolfgang; Kohlhase, Jürgen; Barrionuevo, Francisco

doi:10.2353/ajpath.2008.071039

Cited by 64 publications

(57 citation statements)

References 40 publications

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“…Bohm et al reported that Sall2 knockout mice present strain-dependent neural tube defects (NTD) [4]. In agreement with this and our study, a decrease on SALL2 expression has been linked to neural tube defects induced by valproic acid [5].…”

Section: Introductionsupporting

confidence: 90%

Wild Type p53 Transcriptionally Represses the SALL2 Transcription Factor under Genotoxic Stress

et al. 2013

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SALL2- a member of the Spalt gene family- is a poorly characterized transcription factor found deregulated in various cancers, which suggests it plays a role in the disease. We previously identified SALL2 as a novel interacting protein of neurotrophin receptors and showed that it plays a role in neuronal function, which does not necessarily explain why or how SALL2 is deregulated in cancer. Previous evidences indicate that SALL2 gene is regulated by the WT1 and AP4 transcription factors. Here, we identified SALL2 as a novel downstream target of the p53 tumor suppressor protein. Bioinformatic analysis of the SALL2 gene revealed several putative p53 half sites along the promoter region. Either overexpression of wild-type p53 or induction of the endogenous p53 by the genotoxic agent doxorubicin repressed SALL2 promoter activity in various cell lines. However R175H, R249S, and R248W p53 mutants, frequently found in the tumors of cancer patients, were unable to repress SALL2 promoter activity, suggesting that p53 specific binding to DNA is important for the regulation of SALL2. Electrophoretic mobility shift assay demonstrated binding of p53 to one of the identified p53 half sites in the Sall2 promoter, and chromatin immunoprecipitation analysis confirmed in vivo interaction of p53 with the promoter region of Sall2 containing this half site. Importantly, by using a p53ERTAM knockin model expressing a variant of p53 that is completely dependent on 4-hydroxy-tamoxifen for its activity, we show that p53 activation diminished SALL2 RNA and protein levels during genotoxic cellular stress in primary mouse embryo fibroblasts (MEFs) and radiosensitive tissues in vivo. Thus, our finding indicates that p53 represses SALL2 expression in a context-specific manner, adding knowledge to the understanding of SALL2 gene regulation, and to a potential mechanism for its deregulation in cancer.

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Section: Introductionsupporting

confidence: 90%

Wild Type p53 Transcriptionally Represses the SALL2 Transcription Factor under Genotoxic Stress

et al. 2013

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“…Many of these genes are involved in neurodevelopment and neurogenesis. These include CNP 52 , EN1 45 , ROBO3 53 , ZNRF2 54 , NEUROD1 55 , BMP2 56 , FGF18 57 , SALL1 58 , TULP3 59 , PTEN 60 , ILK 61 , TSC2 62 , CALD1 63 , HOXA3 64 , UTRN 65 , NTF3 66 and EPHB2 67 , among others. Further, additional genes were associated with the development of or risk for various neurological disorders, including autism ( ROBO3 53 , SYN3 and GRIK4 68 ), attention deficit hyperactivity disorder ( ISL1 69 ), Tourette’s syndrome ( SLITRK1 70 ), schizophrenia ( NEUROD1 55 and CYFIP1 71 ), and Alzheimer’s disease ( NQO1 72 and FKBP1B 73 ).…”

Section: 1 Discussionmentioning

confidence: 99%

DNA methylation changes in the placenta are associated with fetal manganese exposure

Maccani

Koestler

Houseman

et al. 2015

Reproductive Toxicology

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Adequate micronutrient intake, including manganese (Mn), is important for fetal development. Both Mn deficiencies and excess exposures are associated with later-life disease, and Mn accumulates in the placenta. Placental functional alterations may alter fetal programming and lifelong health, and we hypothesized that prenatal exposures to Mn may alter placental function through epigenetic mechanisms. Using Illumina’s HumanMethylation450 BeadArray, DNA methylation of >485,000 CpG loci genome-wide was interrogated in 61 placental samples and Mn associations assessed genome-wide via omnibus test (p=0.045). 713 loci were associated with Mn exposure (p<0.0001). 5 significantly differentially-methylated (p<1.3×10−7) loci reside in neurodevelopmental, fetal growth and cancer-related genes. cg22284422, within the uncharacterized LOC284276 gene, was associated with birth weight; for every 10% increase in methylation, lower birth weights were observed, with an average decrease of 293.44 grams. Our observations suggests a link between prenatal micronutrient levels, placental epigenetic status and birth weight, although these preliminary results require validation.

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“…Surprisingly, genes previously considered as neural crest specifiers like FoxD3 and N-myc are transiently coexpressed with pre-neural transcripts before being confined to the neural crest domain (Khudyakov and Bronner-Fraser, 2009) suggesting that at early stages a common regulatory state may define progenitors for both lineages. In addition to Pea3, the Ets transcription factor Erm is now also present in the forming neural plate and the surrounding ectoderm (Lunn et al, 2007) as are Zic1-5 (Elms et al, 2004;Elms et al, 2003;Gamse and Sive, 2001;Inoue et al, 2007;Merzdorf, 2007;Mizuseki et al, 1998;Nakata et al, 1997Nakata et al, , 1998, Dlx3 (in chick; Khudyakov and Bronner-Fraser, 2009), Sall1 (Bohm et al, 2008;Sweetman et al, 2005) and Spalt4 (or Sall4; Barembaum and Bronner-Fraser, 2007). In Xenopus, Zic1 and Zic5 are activated at the edge of the neural plate in response to FGF signalling presumably from the underlying paraxial mesoderm (Hong and Saint-Jeannet, 2007;Monsoro-Burq et al, 2003); in tissue recombination assays paraxial mesoderm can induce Zic5 in animal caps, but this is blocked in caps injected with dominant negative FGF receptor (Monsoro-Burq et al, 2003).…”

Section: Subdivision Of the Ectoderm By Sequential Activation Of Tranmentioning

confidence: 96%

The peripheral sensory nervous system in the vertebrate head: A gene regulatory perspective

Grocott

Tambalo

Streit

2012

Developmental Biology

141

224

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In the vertebrate head, crucial parts of the sense organs and sensory ganglia develop from special regions, the cranial placodes. Despite their cellular and functional diversity, they arise from a common field of multipotent progenitors and acquire distinct identity later under the influence of local signalling. Here we present the gene regulatory network that summarises our current understanding of how sensory cells are specified, how they become different from other ectodermal derivatives and how they begin to diversify to generate placodes with different identities. This analysis reveals how sequential activation of sets of transcription factors subdivides the ectoderm over time into smaller domains of progenitors for the central nervous system, neural crest, epidermis and sensory placodes. Within this hierarchy the timing of signalling and developmental history of each cell population is of critical importance to determine the ultimate outcome. A reoccurring theme is that local signals set up broad gene expression domains, which are further refined by mutual repression between different transcription factors. The Six and Eya network lies at the heart of sensory progenitor specification. In a positive feedback loop these factors perpetuate their own expression thus stabilising pre-placodal fate, while simultaneously repressing neural and neural crest specific factors. Downstream of the Six and Eya cassette, Pax genes in combination with other factors begin to impart regional identity to placode progenitors. While our review highlights the wealth of information available, it also points to the lack information on the cis-regulatory mechanisms that control placode specification and of how the repeated use of signalling input is integrated.

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Sall1, Sall2, and Sall4 Are Required for Neural Tube Closure in Mice

Cited by 64 publications

References 40 publications

Wild Type p53 Transcriptionally Represses the SALL2 Transcription Factor under Genotoxic Stress

Wild Type p53 Transcriptionally Represses the SALL2 Transcription Factor under Genotoxic Stress

DNA methylation changes in the placenta are associated with fetal manganese exposure

The peripheral sensory nervous system in the vertebrate head: A gene regulatory perspective

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