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GEO help: Mouse over screen elements for information. |
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Status |
Public on Mar 31, 2022 |
Title |
BPTF is essential for murine neocortical development |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Chromatin remodeling complexes modulate DNA accessibility permitting neuronal progenitor cells to proliferate and differentiate to form the mammalian neocortex. In the case of BPTF, the major subunit of a chromatin remodelling complex called NURF, mutations leading to its haploinsufficiency have been linked to cause a recently annotated human neurodevelopmental disorder called NEDDFL (Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies). Patients with this syndrome are mainly characterized with microcephaly and intellectual disability. We conditionally knockout (cKO) the Bptf gene during neocortical neurogenesis to analyze its role during embryonic and postnatal brain development. The Bptf cKO animals reveal significant forebrain hypoplasia. During cortical neurogenesis, the cKOs show a reduction in intermediate neuronal progenitor (INP) cells, an increase in apoptosis as well as a prolonged cell cycle of proliferating progenitors. Similarly, the cKOs have decreased proportions of pyramidal neurons expressing Ctip2 and Foxp1. Lastly, our RNA-seq analysis delineates gene pathways deregulated by Bptf’s removal, which are involved in neurogenesis and neuronal differentiation. Our results indicate that Bptf is critical for murine telencephalon neurogenesis. The hypoplasia demonstrated in the mouse model can resemble the microcephaly displayed by the human NEDFFL patients, highlighting the relevance of chromatin remodelling complexes during intricate neural developmental processes.
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Overall design |
BPTF Emx1-Cre P0 forebrain mRNA stranded sequenced libraries
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Contributor(s) |
Zapata G, Picketts DJ |
Citation(s) |
35604347 |
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Submission date |
Jul 19, 2020 |
Last update date |
Jun 30, 2022 |
Contact name |
Dave Picketts |
Phone |
6137378899
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Organization name |
OHRI
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Department |
Regenerative Medicine
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Lab |
Picketts
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Street address |
501 Smyth Road
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City |
Ottawa |
State/province |
Ontario |
ZIP/Postal code |
K1H 8L6 |
Country |
Canada |
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Platforms (2) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (16)
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Relations |
BioProject |
PRJNA647223 |
SRA |
SRP272499 |
Supplementary file |
Size |
Download |
File type/resource |
GSE154700_RAW.tar |
248.2 Mb |
(http)(custom) |
TAR (of H5, SF) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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