[en] Neocortex expansion during human evolution provides a basis for our enhanced cognitive abilities. Yet, which genes implicated in neocortex expansion are actually responsible for higher cognitive abilities is unknown. The expression of human-specific ARHGAP11B in embryonic/foetal mouse, ferret and marmoset neocortex was previously found to promote basal progenitor proliferation, upper-layer neuron generation and neocortex expansion during development, features commonly thought to contribute to increased cognitive abilities. However, a key question is whether this phenotype persists into adulthood and if so, whether cognitive abilities are indeed increased. Here, we generated a transgenic mouse line with physiological ARHGAP11B expression that exhibits increased neocortical size and upper-layer neuron numbers persisting into adulthood. Adult ARHGAP11B-transgenic mice showed altered neurobehaviour, notably increased memory flexibility and a reduced anxiety level. Our data are consistent with the notion that neocortex expansion by ARHGAP11B, a gene implicated in human evolution, underlies some of the altered neurobehavioural features observed in the transgenic mice, such as the increased memory flexibility, a neocortex-associated trait, with implications for the increase in cognitive abilities during human evolution.
Disciplines :
Neurology
Author, co-author :
Xing, Lei ; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Kubik-Zahorodna, Agnieszka ; Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
Namba, Takashi; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Pinson, Anneline ; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Florio, Marta; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Prochazka, Jan; Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
Sarov, Mihail; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Sedlacek, Radislav; Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic
Huttner, Wieland B ; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Language :
English
Title :
Expression of human-specific ARHGAP11B in mice leads to neocortex expansion and increased memory flexibility.
We apologize to all researchers whose work could not be cited due to space limitations. We are grateful to the services and facilities of MPI‐CBG and BIOCEV/IMG for the outstanding support provided, notably Jana Kopkanová and her team of BIOCEV/IMG, as well as Sylke Winkler and her team of the DNA Sequencing and Genotyping Facility, Jussi Helppi and his team of the Biomedical Services, Jan Peychl and his team of the Light Microscopy Facility, Ronald Naumann and his team of the Transgenic Core Facility, Ina Nüßlein, Julia Jarrells and Christina Eugster Oegema of the Cell Technology Facility, Lena Hersemann of the Scientific Computing Facility and the Genome Engineering Facility of MPI‐CBG. RVO 68378050 from Czech Academy of Sciences, LM2018126, CZ.1.05/1.1.00/02.0109 and CZ.1.05/2.1.00/19.0395 for the Czech Center of Phenogenomics were provided to R.S. by MEYS. W.B.H. was supported by grants from the DFG (SFB 655 ‐ A2), the ERC (250197) and ERA‐NET NEURON (MicroKin). Open Access funding enabled and organized by Projekt DEAL.We apologize to all researchers whose work could not be cited due to space limitations. We are grateful to the services and facilities of MPI-CBG and BIOCEV/IMG for the outstanding support provided, notably Jana Kopkanov??and her team of BIOCEV/IMG, as well as Sylke Winkler and her team of the DNA Sequencing and Genotyping Facility, Jussi Helppi and his team of the Biomedical Services, Jan Peychl and his team of the Light Microscopy Facility, Ronald Naumann and his team of the Transgenic Core Facility, Ina N??lein, Julia Jarrells and Christina Eugster Oegema of the Cell Technology Facility, Lena Hersemann of the Scientific Computing Facility and the Genome Engineering Facility of MPI-CBG. RVO 68378050 from Czech Academy of Sciences, LM2018126, CZ.1.05/1.1.00/02.0109 and CZ.1.05/2.1.00/19.0395 for the Czech Center of Phenogenomics were provided to R.S. by MEYS. W.B.H. was supported by grants from the DFG (SFB 655 - A2), the ERC (250197) and ERA-NET NEURON (MicroKin). Open Access funding enabled and organized by Projekt DEAL.
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