The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Direct and concentration-dependent regulation of the proneural gene Neurogenin2 by Pax6
Open accessAbstract
Expression of the proneural gene Neurogenin2 is controlled by several enhancer elements, with the E1 element active in restricted progenitor domains in the embryonic spinal cord and telencephalon that express the homeodomain protein Pax6. We show that Pax6 function is both required and sufficient to activate this enhancer, and we identify one evolutionary conserved sequence in the E1 element with high similarity to a consensus Pax6 binding site. This conserved sequence binds Pax6 protein with low affinity both in vitro and in vivo, and its disruption results in a severe decrease in E1 activity in the spinal cord and in its abolition in the cerebral cortex. The regulation of Neurogenin2 by Pax6 is thus direct. Pax6 is expressed in concentration gradients in both spinal cord and telencephalon. We demonstrate that the E1 element is only activated by high concentrations of Pax6 protein, and that this requirement explains the restriction of E1 enhancer activity to domains of high Pax6 expression levels in the medioventral spinal cord and lateral cortex. By modifying the E1 enhancer sequence, we also show that the spatial pattern of enhancer activity is determined by the affinity of its binding site for Pax6. Together, these data demonstrate that direct transcriptional regulation accounts for the coordination between mechanisms of patterning and neurogenesis. They also provide evidence that Pax6 expression gradients are involved in establishing borders of gene expression domains in different regions of the nervous system.
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Cites
Neuronal specification in the spinal cord: inductive signals and transcriptional codes
Jessell, T. M. (2000) · Nature Reviews Genetics · doi:10.1038/35049541 · Cited by 2,089
The bHLH Transcription Factors OLIG2 and OLIG1 Couple Neuronal and Glial Subtype Specification
Zhou, Q., & Anderson, D. J. (2002) · Cell · doi:10.1016/s0092-8674(02)00677-3 · Cited by 1,059
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Decoding gene regulation in the fly brain
Janssens, J., Aibar, S., Taskiran, I. I., Ismail, J. N., Spanier, K. I., Bravo González-Blas, C., Quan, X. J., Papasokrati, D., Hulselmans, G., Makhzami, S., et al. (2021) · doi:10.1101/2021.08.11.454937 · Cited by 170
Decoding gene regulation in the fly brain
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Regulation of cerebral cortical neurogenesis by the Pax6 transcription factor
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From trans to cis: transcriptional regulatory networks in neocortical development
Shibata, M., Gulden, F. O., & Sestan, N. (2015) · Trends in Genetics · doi:10.1016/j.tig.2014.12.004 · Cited by 109
Sun, J., Rockowitz, S., Xie, Q., Ashery-Padan, R., Zheng, D., & Cvekl, A. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv589 · Cited by 113
Norman, R. X., Ko, H. W., Huang, V., Eun, C. M., Abler, L. L., Zhang, Z., Sun, X., & Eggenschwiler, J. T. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp113 · Cited by 103
Metadata
- Authors
- Scardigli, R., Bäumer, N., Gruss, P., Guillemot, F., & Le Roux, I.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2003-07-15
- Volume
- 130
- Issue
- 14
- Pages
- 3269-3281
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2031482377
- Cited by
- 228
- References
- 2
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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