TY - JOUR
T1 - The Cell-Intrinsic Requirement of Sox6 for Cortical Interneuron Development
AU - Batista-Brito, Renata
AU - Rossignol, Elsa
AU - Hjerling-Leffler, Jens
AU - Denaxa, Myrto
AU - Wegner, Michael
AU - Lefebvre, Véronique
AU - Pachnis, Vassilis
AU - Fishell, Gord
N1 - Funding Information:
Research in the Fishell laboratory is supported by R01MH068469 and R01NS039007 Grants from the NIMH and the NINDS, respectively, as well as generous support from the Simons Foundation. R.B. was funded by Fundacao Ciencia e Tecnologia (FCT). E.R. is funded by the Quebec Health Research Fund (FRSQ). J.H.L. was funded by the Swedish Brain Foundation (Hjärnfonden) postdoctoral grant and is currently an EMBO long-term fellow. We wish to thank Dr. Nicoletta Kessaris for providing the Lhx6 Cre and Nkx2-1 Cre mouse lines; Frank Costatini for providing the R26R YFP line; Takuji Iwasato for his Emx1 Cre ; and Yuchio Yanagawa for his generous gift of his Gad67 EGFP allele. We would like to thank Bernardo Rudy for the generous gift of the antibodies Kv3.1b and Kv3.2. We would also like to thank Lihong Yin for excellent technical help. We thank members of the Fishell laboratory for critically reading this manuscript. We would also like to thank Goichi Miyoshi for generously sharing with us unpublished results.
PY - 2009/8/27
Y1 - 2009/8/27
N2 - We describe the role of Sox6 in cortical interneuron development, from a cellular to a behavioral level. We identify Sox6 as a protein expressed continuously within MGE-derived cortical interneurons from postmitotic progenitor stages into adulthood. Both its expression pattern and null phenotype suggests that Sox6 gene function is closely linked to that of Lhx6. In both Lhx6 and Sox6 null animals, the expression of PV and SST and the position of both basket and Martinotti neurons are abnormal. We find that Sox6 functions downstream of Lhx6. Electrophysiological analysis of Sox6 mutant cortical interneurons revealed that basket cells, even when mispositioned, retain characteristic but immature fast-spiking physiological features. Our data suggest that Sox6 is not required for the specification of MGE-derived cortical interneurons. It is, however, necessary for their normal positioning and maturation. As a consequence, the specific removal of Sox6 from this population results in a severe epileptic encephalopathy.
AB - We describe the role of Sox6 in cortical interneuron development, from a cellular to a behavioral level. We identify Sox6 as a protein expressed continuously within MGE-derived cortical interneurons from postmitotic progenitor stages into adulthood. Both its expression pattern and null phenotype suggests that Sox6 gene function is closely linked to that of Lhx6. In both Lhx6 and Sox6 null animals, the expression of PV and SST and the position of both basket and Martinotti neurons are abnormal. We find that Sox6 functions downstream of Lhx6. Electrophysiological analysis of Sox6 mutant cortical interneurons revealed that basket cells, even when mispositioned, retain characteristic but immature fast-spiking physiological features. Our data suggest that Sox6 is not required for the specification of MGE-derived cortical interneurons. It is, however, necessary for their normal positioning and maturation. As a consequence, the specific removal of Sox6 from this population results in a severe epileptic encephalopathy.
KW - DEVBIO
KW - MOLNEURO
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U2 - 10.1016/j.neuron.2009.08.005
DO - 10.1016/j.neuron.2009.08.005
M3 - Article
C2 - 19709629
AN - SCOPUS:68949157053
SN - 0896-6273
VL - 63
SP - 466
EP - 481
JO - Neuron
JF - Neuron
IS - 4
ER -