Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem Cells
Recent studies indicate that the location of neurogenesis within the medial ganglionic eminence (MGE) critically influences the fate determination of cortical interneuron subgroups, with parvalbumin (Pv) interneurons originating from subventricular zone divisions and somatostatin (Sst) interneurons...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-05-01
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| Series: | Stem Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117301212 |
| _version_ | 1818138256966942720 |
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| author | David J. Tischfield Junho Kim Stewart A. Anderson |
| author_facet | David J. Tischfield Junho Kim Stewart A. Anderson |
| author_sort | David J. Tischfield |
| collection | DOAJ |
| description | Recent studies indicate that the location of neurogenesis within the medial ganglionic eminence (MGE) critically influences the fate determination of cortical interneuron subgroups, with parvalbumin (Pv) interneurons originating from subventricular zone divisions and somatostatin (Sst) interneurons primarily arising from apical divisions. The aPKC-CBP and Notch signaling pathways regulate the transition from apical to basal progenitor and their differentiation into post-mitotic neurons. We find that aPKC inhibition enhances intermediate neurogenesis from stem cell-derived MGE progenitors, resulting in a markedly increased ratio of Pv- to Sst-expressing interneurons. Conversely, inhibition of Notch signaling enriches for Sst subtypes at the expense of Pv fates. These findings confirm that the mode of neurogenesis influences the fate of MGE-derived interneurons and provide a means of further enrichment for the generation of specific interneuron subgroups from pluripotent stem cells. |
| first_indexed | 2024-12-11T10:09:19Z |
| format | Article |
| id | doaj.art-7ee27e73398f4d23b24bbe313fa42b33 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-11T10:09:19Z |
| publishDate | 2017-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-7ee27e73398f4d23b24bbe313fa42b332022-12-22T01:11:49ZengElsevierStem Cell Reports2213-67112017-05-01851135114310.1016/j.stemcr.2017.03.015Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem CellsDavid J. Tischfield0Junho Kim1Stewart A. Anderson2Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085, USADepartment of Psychiatry, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine ARC 517, Philadelphia, PA 19104-5127, USANeuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085, USARecent studies indicate that the location of neurogenesis within the medial ganglionic eminence (MGE) critically influences the fate determination of cortical interneuron subgroups, with parvalbumin (Pv) interneurons originating from subventricular zone divisions and somatostatin (Sst) interneurons primarily arising from apical divisions. The aPKC-CBP and Notch signaling pathways regulate the transition from apical to basal progenitor and their differentiation into post-mitotic neurons. We find that aPKC inhibition enhances intermediate neurogenesis from stem cell-derived MGE progenitors, resulting in a markedly increased ratio of Pv- to Sst-expressing interneurons. Conversely, inhibition of Notch signaling enriches for Sst subtypes at the expense of Pv fates. These findings confirm that the mode of neurogenesis influences the fate of MGE-derived interneurons and provide a means of further enrichment for the generation of specific interneuron subgroups from pluripotent stem cells.http://www.sciencedirect.com/science/article/pii/S2213671117301212cortical interneuronsembryonic stem cellsfate specificationparvalbuminsomatostatinmouseatypical PKCintermediate neurogenesiscyclin D2 |
| spellingShingle | David J. Tischfield Junho Kim Stewart A. Anderson Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem Cells Stem Cell Reports cortical interneurons embryonic stem cells fate specification parvalbumin somatostatin mouse atypical PKC intermediate neurogenesis cyclin D2 |
| title | Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem Cells |
| title_full | Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem Cells |
| title_fullStr | Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem Cells |
| title_full_unstemmed | Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem Cells |
| title_short | Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem Cells |
| title_sort | atypical pkc and notch inhibition differentially modulate cortical interneuron subclass fate from embryonic stem cells |
| topic | cortical interneurons embryonic stem cells fate specification parvalbumin somatostatin mouse atypical PKC intermediate neurogenesis cyclin D2 |
| url | http://www.sciencedirect.com/science/article/pii/S2213671117301212 |
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