Browsing by Subject "neural crest cells"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Ablation of Ezh2 in neural crest cells leads to aberrant enteric nervous system development in mice
    (Public Library of Science, 2018-08-31) Kim, Hana; Langohr, Ingeborg M.; Faisal, Mohammad; McNulty, Margaret; Thorn, Caitlin; Kim, Joomyeong; Anatomy and Cell Biology, School of Medicine
    In the current study, we examined the role of Ezh2 as an epigenetic modifier for the enteric neural crest cell development through H3K27me3. Ezh2 conditional null mice were viable up to birth, but died within the first hour of life. In addition to craniofacial defects, Ezh2 conditional null mice displayed reduced number of ganglion cells in the enteric nervous system. RT-PCR and ChIP assays indicated aberrant up-regulation of Zic1, Pax3, and Sox10 and loss of H3K27me3 marks in the promoter regions of these genes in the myenteric plexus. Overall, these results suggest that Ezh2 is an important epigenetic modifier for the enteric neural crest cell development through repression of Zic1, Pax3, and Sox10.
  • Thumbnail Image
    Item
    HDAC1 and HDAC2 Control the Specification of Neural Crest Cells into Peripheral Glia
    (Society for Neuroscience, 2014-04-23) Jacob, Claire; Lötscher, Pirmin; Engler, Stefanie; Baggiolini, Arianna; Tavares, Sandra Varum; Brügger, Valérie; John, Nessy; Büchmann-Møller, Stine; Snider, Paige L.; Conway, Simon J.; Yamaguchi, Teppei; Matthias, Patrick; Sommer, Lukas; Mantei, Ned; Suter, Ueli; Department of Pediatrics, School of Medicine
    Schwann cells, the myelinating glia of the peripheral nervous system (PNS), originate from multipotent neural crest cells that also give rise to other cells, including neurons, melanocytes, chondrocytes, and smooth muscle cells. The transcription factor Sox10 is required for peripheral glia specification. However, all neural crest cells express Sox10 and the mechanisms directing neural crest cells into a specific lineagearepoorlyunderstood.Weshowherethathistonedeacetylases1and2(HDAC1/2)areessentialforthespecificationofneuralcrest cells into Schwann cell precursors and satellite glia, which express the early determinants of their lineage myelin protein zero (P0) and/or fatty acid binding protein 7 (Fabp7). In neural crest cells, HDAC1/2 induced expression of the transcription factor Pax3 by binding and activating the Pax3 promoter. In turn, Pax3 was required to maintain high Sox10 levels and to trigger expression of Fabp7. In addition, HDAC1/2 were bound to the P0 promoter and activated P0 transcription. Consistently, in vivo genetic deletion of HDAC1/2 in mouse neuralcrestcellsledtostronglydecreasedSox10expression,nodetectablePax3,virtuallynosatelliteglia,andnoSchwanncellprecursors in dorsal root ganglia and peripheral nerves. Similarly, in vivo ablation of Pax3 in the mouse neural crest resulted in strongly reduced expression of Sox10 and Fabp7. Therefore, by controlling the expression of Pax3 and the concerted action of Pax3 and Sox10 on their target genes, HDAC1/2 direct the specification of neural crest cells into peripheral glia.
  • Thumbnail Image
    Item
    Mandibular and Neural Crest Cell Deficits Seen in TsDn65 Down Syndrome Mouse Model Rescued By Green Tea Polyphenol, EGCG
    (Office of the Vice Chancellor for Research, 2013-04-05) Bose, Gracelyn C.; Novack, Rachel A.; Tumbleson, Danika M.; Chom, Alexis N.; Deitz, Samantha L.
    Down Syndrome (DS) is caused by trisomy of the human chromosome 21 (Hsa21) and occurs in ~1 of every 700 births. DS is distinguished by over 80 phenotypic abnormalities including skeletal deficits and craniofacial phenotypes characterized by a flattened skull, slanted eyes, and a smaller mandible. To study these abnormalities, we utilize the Ts65Dn DS mouse model containing a triplication of approximately half of the gene homologues found on Hsa21 and mirrors the skeletal and mandibular phenotypes observed in DS. In Ts65Dn mice, the origin of the mandibular deficits were traced to a reduction in size of the 1st branchial arch (BA1), the developmental precursor to the mandible, occurring at embryonic day 9.5 (E9.5). At E9.5, we observe a lack of proliferation and migration of neural crest cells (NCC) from the neural tube (NT) into the BA1, causing a reduced BA1. We hypothesize that an overexpression of Dyrk1a, a Hsa21 homologue, contributes to the mandibular deficit seen in E9.5 Ts65Dn embryos. We propose that EGCG, a green tea polyphenol, will inhibit DYRK1a activity, rescuing the BA1 deficit. To test our hypothesis, Ts65Dn mothers were treated with EGCG from E0-E9.5 and sacrificed to retrieve the E9.5 embryos. Our results from unbiased stereological assessments show that E0-E9.5 EGCG in vivo treatment has the potential to increase NCC number, BA1 volume, and embryo volume of trisomic embryos. This data provide preclinical testing for a potential therapy of DS craniofacial disorders, which may extend to treating bone deficits in DS and osteoporosis.