Transcriptional regulation of intermediate progenitor cell generation during hippocampal development

Harris, Lachlan, Zalucki, Oressia, Gobius, Ilan, McDonald, Hannah, Osinki, Jason, Harvey, Tracey J., Essebier, Alexandra, Vidovic, Diana, Gladwyn-Ng, Ivan, Burne, Thomas H., Heng, Julian I., Richards, Linda J., Gronostajski, Richard M. and Piper, Michael (2016) Transcriptional regulation of intermediate progenitor cell generation during hippocampal development. Development, 143 24: 4620-4630. doi:10.1242/dev.140681

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Author Harris, Lachlan
Zalucki, Oressia
Gobius, Ilan
McDonald, Hannah
Osinki, Jason
Harvey, Tracey J.
Essebier, Alexandra
Vidovic, Diana
Gladwyn-Ng, Ivan
Burne, Thomas H.
Heng, Julian I.
Richards, Linda J.
Gronostajski, Richard M.
Piper, Michael
Title Transcriptional regulation of intermediate progenitor cell generation during hippocampal development
Journal name Development   Check publisher's open access policy
ISSN 1477-9129
Publication date 2016-12-13
Sub-type Article (original research)
DOI 10.1242/dev.140681
Open Access Status File (Publisher version)
Volume 143
Issue 24
Start page 4620
End page 4630
Total pages 11
Place of publication Cambridge, United Kingdom
Publisher Company of Biologists
Language eng
Formatted abstract
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.
Keyword Hippocampus
Intermediate progenitor cell
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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