Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages
The enteric nervous system (ENS) predominantly originates from vagal neural crest (VNC) cells that emerge from the caudal hindbrain, invade the foregut and populate the gastrointestinal tract. However, the gene regulatory network (GRN) orchestrating the early specification of VNC remains unknown. Us...
| Príomhchruthaitheoirí: | , |
|---|---|
| Formáid: | Journal article |
| Teanga: | English |
| Foilsithe / Cruthaithe: |
Springer Nature
2019
|
| Ábhair: |
| _version_ | 1826309161851289600 |
|---|---|
| author | Ling, ITC Sauka-Spengler, T |
| author_facet | Ling, ITC Sauka-Spengler, T |
| author_sort | Ling, ITC |
| collection | OXFORD |
| description | The enteric nervous system (ENS) predominantly originates from vagal neural crest (VNC) cells that emerge from the caudal hindbrain, invade the foregut and populate the gastrointestinal tract. However, the gene regulatory network (GRN) orchestrating the early specification of VNC remains unknown. Using an EdnrB enhancer, we generated a comprehensive temporal map of the chromatin and transcriptional landscape of VNC in the avian model, revealing three VNC cell clusters (neural, neurogenic and mesenchymal), each predetermined epigenetically prior to neural tube delamination. We identify and functionally validate regulatory cores (Sox10/Tfap2B/SoxB/Hbox) mediating each programme and elucidate their combinatorial activities with other spatiotemporally specific transcription factors (bHLH/NR). Our global deconstruction of the VNC-GRN in vivo sheds light on critical early regulatory mechanisms that may influence the divergent neural phenotypes in enteric neuropathies. |
| first_indexed | 2024-03-07T07:31:31Z |
| format | Journal article |
| id | oxford-uuid:33771a99-5bd3-482d-b0b4-c553d9f59eb3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:31:31Z |
| publishDate | 2019 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:33771a99-5bd3-482d-b0b4-c553d9f59eb32023-01-20T16:29:59ZEarly chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineagesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:33771a99-5bd3-482d-b0b4-c553d9f59eb3CRISPR-Cas systemsGene regulatory networksDevelopmental biologyEpigenomicsTranscriptional regulatory elementsEnglishSymplectic ElementsSpringer Nature2019Ling, ITCSauka-Spengler, TThe enteric nervous system (ENS) predominantly originates from vagal neural crest (VNC) cells that emerge from the caudal hindbrain, invade the foregut and populate the gastrointestinal tract. However, the gene regulatory network (GRN) orchestrating the early specification of VNC remains unknown. Using an EdnrB enhancer, we generated a comprehensive temporal map of the chromatin and transcriptional landscape of VNC in the avian model, revealing three VNC cell clusters (neural, neurogenic and mesenchymal), each predetermined epigenetically prior to neural tube delamination. We identify and functionally validate regulatory cores (Sox10/Tfap2B/SoxB/Hbox) mediating each programme and elucidate their combinatorial activities with other spatiotemporally specific transcription factors (bHLH/NR). Our global deconstruction of the VNC-GRN in vivo sheds light on critical early regulatory mechanisms that may influence the divergent neural phenotypes in enteric neuropathies. |
| spellingShingle | CRISPR-Cas systems Gene regulatory networks Developmental biology Epigenomics Transcriptional regulatory elements Ling, ITC Sauka-Spengler, T Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages |
| title | Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages |
| title_full | Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages |
| title_fullStr | Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages |
| title_full_unstemmed | Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages |
| title_short | Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages |
| title_sort | early chromatin shaping predetermines multipotent vagal neural crest into neural neuronal and mesenchymal lineages |
| topic | CRISPR-Cas systems Gene regulatory networks Developmental biology Epigenomics Transcriptional regulatory elements |
| work_keys_str_mv | AT lingitc earlychromatinshapingpredeterminesmultipotentvagalneuralcrestintoneuralneuronalandmesenchymallineages AT saukaspenglert earlychromatinshapingpredeterminesmultipotentvagalneuralcrestintoneuralneuronalandmesenchymallineages |