Transcriptional regulation of intermediate progenitor cell generation during hippocampal development

© 2016. Published by The Company of Biologists Ltd. During forebrain development, radial glia generate neurons through the production of intermediate progenitor cells (IPCs). The production of IPCs is a central tenet underlying the generation of the appropriate number of cortical neurons, but the tr...

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Main Authors: Harris, L., Zalucki, O., Gobius, I., McDonald, H., Osinki, J., Harvey, T., Essebier, A., Vidovic, D., Gladwyn-Ng, I., Burne, T., Heng, Julian, Richards, L., Gronostajski, R., Piper, M.
Format: Journal Article
Published: Company of Biologists LTD 2016
Online Access:http://hdl.handle.net/20.500.11937/72230
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author Harris, L.
Zalucki, O.
Gobius, I.
McDonald, H.
Osinki, J.
Harvey, T.
Essebier, A.
Vidovic, D.
Gladwyn-Ng, I.
Burne, T.
Heng, Julian
Richards, L.
Gronostajski, R.
Piper, M.
author_facet Harris, L.
Zalucki, O.
Gobius, I.
McDonald, H.
Osinki, J.
Harvey, T.
Essebier, A.
Vidovic, D.
Gladwyn-Ng, I.
Burne, T.
Heng, Julian
Richards, L.
Gronostajski, R.
Piper, M.
author_sort Harris, L.
building Curtin Institutional Repository
collection Online Access
description © 2016. Published by The Company of Biologists Ltd. During forebrain development, radial glia generate neurons through the production of intermediate progenitor cells (IPCs). The production of IPCs is a central tenet underlying the generation of the appropriate number of cortical neurons, but the transcriptional logic underpinning this process remains poorly defined. Here, we examined IPC production using mice lacking the transcription factor nuclear factor I/X (Nfix). We show that Nfix deficiency delays IPC production and prolongs the neurogenic window, resulting in an increased number of neurons in the postnatal forebrain. Loss of additional Nfi alleles (Nfib) resulted in a severe delay in IPC generation while, conversely, overexpression of NFIX led to precocious IPC generation. Mechanistically, analyses of microarray and ChIP-seq datasets, coupled with the investigation of spindle orientation during radial glial cell division, revealed that NFIX promotes the generation of IPCs via the transcriptional upregulation of inscuteable (Insc). These data thereby provide novel insights into the mechanisms controlling the timely transition of radial glia into IPCs during forebrain development.
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spelling curtin-20.500.11937-722302018-12-13T09:33:30Z Transcriptional regulation of intermediate progenitor cell generation during hippocampal development Harris, L. Zalucki, O. Gobius, I. McDonald, H. Osinki, J. Harvey, T. Essebier, A. Vidovic, D. Gladwyn-Ng, I. Burne, T. Heng, Julian Richards, L. Gronostajski, R. Piper, M. © 2016. Published by The Company of Biologists Ltd. During forebrain development, radial glia generate neurons through the production of intermediate progenitor cells (IPCs). The production of IPCs is a central tenet underlying the generation of the appropriate number of cortical neurons, but the transcriptional logic underpinning this process remains poorly defined. Here, we examined IPC production using mice lacking the transcription factor nuclear factor I/X (Nfix). We show that Nfix deficiency delays IPC production and prolongs the neurogenic window, resulting in an increased number of neurons in the postnatal forebrain. Loss of additional Nfi alleles (Nfib) resulted in a severe delay in IPC generation while, conversely, overexpression of NFIX led to precocious IPC generation. Mechanistically, analyses of microarray and ChIP-seq datasets, coupled with the investigation of spindle orientation during radial glial cell division, revealed that NFIX promotes the generation of IPCs via the transcriptional upregulation of inscuteable (Insc). These data thereby provide novel insights into the mechanisms controlling the timely transition of radial glia into IPCs during forebrain development. 2016 Journal Article http://hdl.handle.net/20.500.11937/72230 10.1242/dev.140681 Company of Biologists LTD restricted
spellingShingle Harris, L.
Zalucki, O.
Gobius, I.
McDonald, H.
Osinki, J.
Harvey, T.
Essebier, A.
Vidovic, D.
Gladwyn-Ng, I.
Burne, T.
Heng, Julian
Richards, L.
Gronostajski, R.
Piper, M.
Transcriptional regulation of intermediate progenitor cell generation during hippocampal development
title Transcriptional regulation of intermediate progenitor cell generation during hippocampal development
title_full Transcriptional regulation of intermediate progenitor cell generation during hippocampal development
title_fullStr Transcriptional regulation of intermediate progenitor cell generation during hippocampal development
title_full_unstemmed Transcriptional regulation of intermediate progenitor cell generation during hippocampal development
title_short Transcriptional regulation of intermediate progenitor cell generation during hippocampal development
title_sort transcriptional regulation of intermediate progenitor cell generation during hippocampal development
url http://hdl.handle.net/20.500.11937/72230