Combination of in silico and in situ hybridisation approaches to identify potential Dll1 associated miRNAs during mouse embryogenesis

Hoesel, Bastian; Bhujabal, Zambarlal; Przemeck, Gerhard K. H.; Kurz-Drexler, Annerose; Weisenhorn, Daniela M. Vogt; Angelis, Martin Hrabé de; Beckers, Johannes

doi:10.1016/j.gep.2010.06.002

Cited by 17 publications

(16 citation statements)

References 33 publications

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“…93 Thus, miR-449 targets a receptor (Notch1) and a ligand (DLL1), allowing the reduction of Notch signaling and lateral inhibition from both interacting cells. Notch inactivation by miR-449 is expected to release transcriptional repression from genes necessary for differentiation; the exact targets and their precise mechanistic role remain obscure.…”

mentioning

confidence: 99%

MicroRNA-449 in cell fate determination

Lizé¹,

Klimke²,

Dobbelstein³

2011

Cell Cycle

124

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confidence: 99%

MicroRNA-449 in cell fate determination

Lizé¹,

Klimke²,

Dobbelstein³

2011

Cell Cycle

124

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“…The overexpression of the miR-23a-27a-24-2 cluster can induce apoptosis by creating stress on the endoplasmic reticulum (Chhabra et al, 2011). miR-34a, miR-103, miR-107, miR-130a, miR-130b, miR-449a, and miR-449c are partially complementary to the 3'-untranslated regions of gene Dll1, and participate in the regulation of Dll1 expression in the paraxial and the limb mesoderm, the NT and the hindbrain region, and in the cranial ganglia (Hoesel et al, 2010). The overexpression of miR-34a during NT development can result in an NTD by inducing Dll1 downregulation, which leads to a prolonged state of ventral progenitor expression instead of appropriately timed differentiation (Shookhoff and Gallicano, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…For instance, the altered expression of a subset of discrete miRNAs is involved in NTD generation in p532/2 embryos, which subsequently exhibit exencephaly (Hosako et al, 2009). Several miRNAs are expressed during the murine NT development and directly target genes that are important for NT ontogenesis (Hoesel et al, 2010). These studies, therefore, suggest that miRNAs are involved in CNS development, including in NT development.…”

Section: Introductionmentioning

confidence: 93%

MicroRNAs function primarily in the pathogenesis of human anencephaly via the mitogen-activated protein kinase signaling pathway

Zhang¹,

Yu²,

Fu³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Anencephaly is one of the most serious forms of neural tube defects (NTDs), a group of congenital central nervous system (CNS) malformations. MicroRNAs (miRNAs) are involved in diverse biological processes via the post-transcriptional regulation of target mRNAs. Although miRNAs play important roles in the development of mammalian CNS, their function in human NTDs remains unknown. Using a miRNA microarray, we identified a unique expression profile in fetal anencephalic brain tissues, characterized by 70 upregulated miRNAs (ratio ≥2) and 7 downregulated miRNAs (ratio ≤0.5) compared with healthy human samples. Ten miRNAs with altered expression were selected from the microarray findings for validation with real-time quantitative reverse transcription-polymerase chain reaction. We found that in anencephalic tissues, miR-22, miR23a, miR-34a, miR-103, miR-125a, miR-132, miR-134, miR-138, and miR-185 were significantly upregulated, while miR-149 was significantly downregulated. Furthermore, 459 potential target genes within the validated miRNAs were revealed using combined four target prediction algorithms in the human genome, and subsequently analyzed with the Molecule Annotation System 3.0. A total of 119 target genes were ultimately identified, including those involved in 22 singular annotations (i.e., transcription, signal transduction, and cell cycle) and 55 functional pathways [i.e., mitogen-activated protein kinase (MAPK) signaling pathway, and actin cytoskeleton regulation]. Six target genes (HNRPU, JAG1, FMR1, EGR3, RUNX1T1, and NDEL1) were chosen as candidate genes and associated with congenital birth abnormalities of the brain structure. Our results, therefore, suggest that miRNA maladjustment mainly contributes to the etiopathogenesis of anencephaly via the MAPK signaling pathway.

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“…It is now well established that miRNAs are critical regulators of proliferation, differentiation, and apoptosis during embryogenesis (for review see, (O’Rourke et al, 2006; Yang and Wu, 2006)), however their role in neural tube development has only recently begun to be examined (Chakrabarty et al, 2007; Song and Tuan, 2006; Wienholds et al, 2005). Indeed, in a recent study, several miRNAs were documented to be expressed in the developing murine neural tube and to target genes crucial for neural tube ontogenesis (Hoesel et al, 2010). Moreover, examination of p53 −/− embryos, exhibiting exencephaly, revealed altered expression of a subset of discrete miRNAs implying their involvement in this NTD (Hosako et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA gene expression signatures in the developing neural tube

Mukhopadhyay¹,

Brock²,

Appana³

et al. 2011

Birth Defects Research

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BACKGROUND Neurulation requires precise, spatio-temporal expression of numerous genes and coordinated interaction of signal transduction and gene regulatory networks, disruption of which may contribute to the etiology of neural tube (NT) defects. MicroRNAs are key modulators of cell and tissue differentiation. In order to define potential roles of miRNAs in development of the murine NT, miRNA microarray analysis was conducted to establish expression profiles, and identify miRNA target genes and functional gene networks. METHODS miRNA expression profiles in murine embryonic NTs derived from gestational days 8.5, 9.0 and 9.5 were defined and compared utilizing miRXplore™ microarrays from Miltenyi Biotech GmbH. Gene expression changes were verified by TaqMan™ quantitative Real-Time PCR. clValid R package and the UPGMA (hierarchical) clustering method were utilized for cluster analysis of the microarray data. Functional associations among selected miRNAs were examined via Ingenuity Pathway Analysis. RESULTS miRXplore™ chips enabled examination of 609 murine miRNAs. Expression of approximately 12% of these was detected in murine embryonic NTs. Clustering analysis revealed several developmentally regulated expression clusters among these expressed genes. Target analysis of differentially expressed miRNAs enabled identification of numerous target genes associated with cellular processes essential for normal NT development. Utilization of Ingenuity Pathway Analysis revealed interactive biological networks which connected differentially expressed miRNAs with their target genes, and highlighted functional relationships. CONCLUSIONS The present study defined unique gene expression signatures of a range of miRNAs in the developing NT during the critical period of NT morphogenesis. Analysis of miRNA target genes and gene interaction pathways revealed that specific miRNAs may direct expression of numerous genes encoding proteins which have been shown to be indispensable for normal neurulation. This study is the first to identify miRNA expression profiles and their potential regulatory networks in the developing mammalian NT.

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Combination of in silico and in situ hybridisation approaches to identify potential Dll1 associated miRNAs during mouse embryogenesis

Cited by 17 publications

References 33 publications

MicroRNA-449 in cell fate determination

MicroRNA-449 in cell fate determination

MicroRNAs function primarily in the pathogenesis of human anencephaly via the mitogen-activated protein kinase signaling pathway

MicroRNA gene expression signatures in the developing neural tube

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