Abstract
Key facets of mammalian forebrain cortical development include the radial migration of projection neurons and subsequent cellular differentiation into layer-specific subtypes. Inappropriate regulation of these processes can lead to a number of congenital brain defects in both mouse and human, including lissencephaly and intellectual disability. The genes regulating these processes are still not all identified, suggesting genetic analyses will continue to be a powerful tool in mechanistically studying the development of the cerebral cortex. Reelin is a molecule which we have understood to be critical for proper cortical development for many years. The precise mechanism of Reelin, however, is not fully understood. To address both of these unresolved issues, we report here the creation of a novel conditional allele of the Reelin gene and showcase the use of an Etv1-GFP transgenic line highlighting a subpopulation of the cortex: layer V pyramidal neurons. Together, these represent genetic tools which may facilitate the study of cortical development in a number of different ways.
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Acknowledgments
This work was supported by the Cincinnati Children’s Research Foundation and the NINDS (R01NS085023). We thank members of the Stottmann lab for critical review of this manuscript. The ES cells used for this research project were generated by the trans-NIH Knockout Mouse Project (KOMP) and obtained from the KOMP Repository (www.komp.org). NIH grants to Velocigene at Regeneron Inc (U01HG004085) and the CSD Consortium (U01HG004080) funded the generation of gene-targeted ES cells for 8500 genes in the KOMP Program and archived and distributed by the KOMP Repository at UC Davis and CHORI (U42RR024244). We are grateful to Renee Araiza at the Mouse Biology Program, UC Davis for obtaining primary data from KOMP on the construction of the reelin gene trap allele.
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Megan Cionni and Chelsea Menke contributed equally.
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335_2015_9615_MOESM1_ESM.tiff
Figure S1. Correct genomic targeting of the Reln tm1a allele. (A) Long-range PCR genotyping to show targeted insertion of the gene trap cassette in the reelin locus (relative primer locations are shown in Fig. 1A) with two distinct 5′ primers. (B) PCR genotyping designed to indicate both genomic integrity of the locus (7 kb product) and vector integrity (2 kb). (C) PCR genotyping to confirm 3′ loxP site integration. All data in are from the KOMP project at UC Davis. Supplementary material 1 (TIFF 1521 kb)
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Cionni, M., Menke, C. & Stottmann, R.W. Novel genetic tools facilitate the study of cortical neuron migration. Mamm Genome 27, 8–16 (2016). https://doi.org/10.1007/s00335-015-9615-6
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DOI: https://doi.org/10.1007/s00335-015-9615-6