ArticleNeural development2016
Expression and functional analysis of the Wnt/beta-catenin induced mir-135a-2 locus in embryonic forebrain development.
Article in Neural development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Lmx1a is a master regulator of the cortical hem.eLife · 2023Article
- Circulating miRNAs in maternal plasma as potential biomarkers of early pregnancy in sheep.Frontiers in genetics · 2022Article
- miRNA-independent function of long noncoding pri-miRNA loci.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Analysis of mir-9 Expression Pattern in Rat Retina during Postnatal Development.International journal of molecular sciences · 2021Article
- Variations of telencephalic development that paved the way for neocortical evolution.Progress in neurobiology · 2020Review
- Noncoding RNAs and Midbrain DA Neurons: Novel Molecular Mechanisms and Therapeutic Targets in Health and Disease.Biomolecules · 2020Review
- Silencing of RIPK4 inhibits epithelial‑mesenchymal transition by inactivating the Wnt/β‑catenin signaling pathway in osteosarcoma.Molecular medicine reports · 2020Article
- A Balanced Translocation in Kallmann Syndrome Implicates a Long Noncoding RNA, RMST, as a GnRH Neuronal Regulator.The Journal of clinical endocrinology and metabolism · 2020Article
- Antagonizing IncreasedThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition.The Journal of biological chemistry · 2018Article
- Egr2-dependent microRNA-138 is dispensable for peripheral nerve myelination.Scientific reports · 2018Article
- An Image-Based miRNA Screen Identifies miRNA-135s As Regulators of CNS Axon Growth and Regeneration by Targeting Krüppel-like Factor 4.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Genome-wide analysis and functional prediction of long non-coding RNAs in mouse uterus during the implantation window.Oncotarget · 2017Article
- A novel floor plate boundary defined by adjacent En1 and Dbx1 microdomains distinguishes midbrain dopamine and hypothalamic neurons.Development (Cambridge, England) · 2017Article
- Understanding the Role of lncRNAs in Nervous System Development.Advances in experimental medicine and biology · 2017Review
- CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells.Molecular autism · 2017Article
- Association of tumor and plasma microRNA expression with tumor monosomy-3 in patients with uveal melanoma.Clinical epigenetics · 2016Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBrain size and patterning are dependent on dosage-sensitive morphogen signaling pathways - yet how these pathways are calibrated remains enigmatic. Recent studies point to a new role for microRNAs in tempering the spatio-temporal range of morphogen functions during development. Here, we investigated the role of miR-135a, derived from the mir-135a-2 locus, in embryonic forebrain development.
method1. We characterized the expression of miR-135a, and its host gene Rmst, by in situ hybridization (ish). 2. We conditionally ablated, or activated, beta-catenin in the dorsal forebrain to determine if this pathway was necessary and/or sufficient for Rmst/miR-135a expression. 3. We performed bioinformatics analysis to unveil the most predicted pathways targeted by miR-135a. 4. We performed gain and loss of function experiments on mir-135a-2 and analyzed by ish the expression of key markers of cortical hem, choroid plexus, neocortex and hippocampus.
results1. miR-135a, embedded in the host long non-coding transcript Rmst, is robustly expressed, and functional, in the medial wall of the embryonic dorsal forebrain, a Wnt and TGFβ/BMP-rich domain. 2. Canonical Wnt/beta-catenin signaling is critical for the expression of Rmst and miR-135a, and the cortical hem determinant Lmx1a. 3. Bioinformatics analyses reveal that the Wnt and TGFβ/BMP cascades are among the top predicted pathways targeted by miR-135a. 4. Analysis of mir-135a-2 null embryos showed that dorsal forebrain development appeared normal. In contrast, modest mir-135a-2 overexpression, in the early dorsal forebrain, resulted in a phenotype resembling that of mutants with Wnt and TGFβ/BMP deficits - a smaller cortical hem and hippocampus primordium associated with a shorter neocortex as well as a less convoluted choroid plexus. Interestingly, late overexpression of mir-135a-2 revealed no change.
conclusionsAll together, our data suggests the existence of a Wnt/miR-135a auto-regulatory loop, which could serve to limit the extent, the duration and/or intensity of the Wnt and, possibly, the TGFβ/BMP pathways.
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