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Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
Basic helix-loop-helix transcription factors cooperate to specify a cortical projection neuron identity
Pierre Mattar1, Lisa Marie Langevin, Kathryn Markham
1Institute of Maternal and Child Health, Hotchkiss Brain Institute, University of Calgary, 2277 HSC, 3330 Hospital Dr. NW, Calgary, Alberta, Canada.
Molecular and Cellular Biology
|December 28, 2007
Summary
The proneural gene Ngn2 instructs cortical neuron identity. It works faster in the dorsal telencephalon, aided by the bHLH gene Math3, to control gene expression timing.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Cortical projection neuron identity is determined by transcription factors.
- The precise roles and downstream effects of these factors are not fully understood.
Purpose of the Study:
- To investigate the instructive versus permissive roles of transcription factors in cortical neuron development.
- To elucidate the downstream genetic cascades regulated by Ngn2.
- To understand regional differences in Ngn2 function within the telencephalon.
Main Methods:
- Misexpression of the proneural basic helix-loop-helix (bHLH) gene Ngn2 in ventral telencephalic progenitors.
- Temporal analysis of ectopic marker gene expression.
- Identification of Ngn2 transcriptional targets using molecular assays.
- In vivo luciferase assays to measure transcriptional drive.
Main Results:
- Ngn2 misexpression induced a temporal sequence of cortical marker expression (Nscl2, BhlhB5, NeuroD, NeuroD2, Math2, Tbr1).
- Ngn2 induced cortical gene expression more rapidly in the dorsal than ventral telencephalon.
- Math3 was identified as a dorsally restricted Ngn2 target and cofactor that synergizes with Ngn2.
- Ngn2 exhibited lower transcriptional drive in ventral compared to dorsal telencephalic domains, an effect augmented by Math3.
Conclusions:
- Ngn2 instructs partial cortical identity and initiates downstream genetic cascades in a temporal manner.
- Regional differences in Ngn2 function are mediated by Math3 and transcriptional strength.
- Cooperation among cortical bHLH genes regulates transcriptional strength and temporal gene expression coordination.
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