TY - JOUR
T1 - Generation of Cre-transgenic mice using Dlx1/Dlx2 enhancers and their characterization in GABAergic interneurons
AU - Potter, Gregory B.
AU - Petryniak, Magdalena A.
AU - Shevchenko, Eugenia
AU - McKinsey, Gabriel L.
AU - Ekker, Marc
AU - Rubenstein, John L.R.
N1 - Funding Information:
UCSF Comprehensive Cancer Center Transgenic Core performed the oocyte injections and generated the I12b-Cre and URE2-Cre transgenic mice. Louis Reichardt, Ben Cheyette and the Nikon Imaging Center at UCSF provided access to microscopes used in this study. We would like to thank M. Wegner for the SOX10 antibody, K. Yoshikawa for DLX2 antibody, and C. Stiles for OLIG1 and OLIG2 antibodies. We thank N. Ghanem for providing data prior to publication. G.B.P. made the I12b-Cre and URE2-Cre transgenes, characterized the different lines of I12b-Cre and URE2-Cre transgenic mice, maintained the mouse colonies, designed and implemented the experiments, photographed and quantified brain sections, performed statistical analysis on the data, wrote the manuscript, and prepared all tables and figures. M.A.P. helped with experimental design, interpreted the data, and prepared, sectioned, immunolabeled and photographed brain tissue. E.S. genotyped and maintained transgenic mice, sectioned, immunolabeled and photographed tissue, and quantified the birth-date data. G.L.M. performed the ChIP experiments. M.E. provided plasmids containing I12b and URE2 DNA, feedback on transgene construction, and comments on the manuscript. J.L.R. provided mentorship on experimental design, analysis, and manuscript preparation. G.B.P. was supported by the California Institute of Regenerative Medicine's Postdoctoral Fellowship; M.A.P. was funded in part by NICHD HD-07162H; M.E. was supported by CIHR grant #MOP-14460; JLR was supported by Nina Ireland, NIMH RO1 MH49428 and K05 MH065670.
PY - 2009/2
Y1 - 2009/2
N2 - DLX1 and DLX2 transcription factors are necessary for forebrain GABAergic neuron differentiation, migration, and survival. We generated transgenic mice that express Cre-recombinase under the control of two ultra-conserved DNA elements near the Dlx1 and 2 locus termed I12b and URE2. We show that Cre-recombinase is active in a "Dlx-pattern" in the embryonic forebrain of transgenic mice. I12b-Cre is more active than URE2-Cre in the medial ganglionic eminences and its derivatives. Fate-mapping of EGFP+ cells in adult Cre;Z/EG animals demonstrated that GABAergic neurons, but not glia, are labeled. Most NPY+, nNOS+, parvalbumin+, and somatostatin+ cells are marked by I12b-Cre in the cortex and hippocampus, while 25-40% of these interneuron subtypes are labeled by URE2-Cre. Labeling of neurons generated between E12.5 to E15.5 indicated differences in birth-dates of EGFP+ cells that populate the olfactory bulb, hippocampus, and cortex. Finally, we provide the first in vivo evidence that both I12b and URE2 are direct targets of DLX2 and require Dlx1 and Dlx2 expression for proper activity.
AB - DLX1 and DLX2 transcription factors are necessary for forebrain GABAergic neuron differentiation, migration, and survival. We generated transgenic mice that express Cre-recombinase under the control of two ultra-conserved DNA elements near the Dlx1 and 2 locus termed I12b and URE2. We show that Cre-recombinase is active in a "Dlx-pattern" in the embryonic forebrain of transgenic mice. I12b-Cre is more active than URE2-Cre in the medial ganglionic eminences and its derivatives. Fate-mapping of EGFP+ cells in adult Cre;Z/EG animals demonstrated that GABAergic neurons, but not glia, are labeled. Most NPY+, nNOS+, parvalbumin+, and somatostatin+ cells are marked by I12b-Cre in the cortex and hippocampus, while 25-40% of these interneuron subtypes are labeled by URE2-Cre. Labeling of neurons generated between E12.5 to E15.5 indicated differences in birth-dates of EGFP+ cells that populate the olfactory bulb, hippocampus, and cortex. Finally, we provide the first in vivo evidence that both I12b and URE2 are direct targets of DLX2 and require Dlx1 and Dlx2 expression for proper activity.
UR - http://www.scopus.com/inward/record.url?scp=59049084993&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59049084993&partnerID=8YFLogxK
U2 - 10.1016/j.mcn.2008.10.003
DO - 10.1016/j.mcn.2008.10.003
M3 - Article
C2 - 19026749
AN - SCOPUS:59049084993
SN - 1044-7431
VL - 40
SP - 167
EP - 186
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 2
ER -