Species-specific maturation profiles of human, chimpanzee and bonobo neural cells

Comparative analyses of neuronal phenotypes in closely related species can shed light on neuronal changes occurring during evolution. The study of post-mortem brains of nonhuman primates (NHPs) has been limited and often does not recapitulate important species-specific developmental hallmarks. We utilize induced pluripotent stem cell (iPSC) technology to investigate the development of cortical pyramidal neurons following migration and maturation of cells grafted in the developing mouse cortex. Our results show differential migration patterns in human neural progenitor cells compared to those of chimpanzees and bonobos both in vitro and in vivo, suggesting heterochronic changes in human neurons. The strategy proposed here lays the groundwork for further comparative analyses between humans and NHPs and opens new avenues for understanding the differences in the neural underpinnings of cognition and neurological disease susceptibility between species.

[1]  Sara B. Linker,et al.  BrainImageR: spatiotemporal gene set analysis referencing the human brain , 2019, Bioinform..

[2]  P. Hof,et al.  Dendritic morphology of pyramidal neurons in the chimpanzee neocortex: regional specializations and comparison to humans. , 2013, Cerebral cortex.

[3]  B. Nickel,et al.  Transcriptional neoteny in the human brain , 2009, Proceedings of the National Academy of Sciences.

[4]  E. Uemura,et al.  Age-related changes in prefrontal cortex of Macaca mulatta: Quantitative analysis of dendritic branching patterns , 1980, Experimental Neurology.

[5]  B. Connors,et al.  Intrinsic firing patterns of diverse neocortical neurons , 1990, Trends in Neurosciences.

[6]  I. Weiler,et al.  Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. , 2001, American journal of medical genetics.

[7]  J. Jacobs,et al.  Regional dendritic and spine variation in human cerebral cortex: a quantitative golgi study. , 2001, Cerebral cortex.

[8]  G. Šimić,et al.  Extraordinary neoteny of synaptic spines in the human prefrontal cortex , 2011, Proceedings of the National Academy of Sciences.

[9]  J. C. Redmond,et al.  Early hominid brain evolution: a new look at old endocasts. , 2000, Journal of human evolution.

[10]  I. Kostović,et al.  Prenatal development of neurons in the human prefrontal cortex. II. A quantitative Golgi study , 1992, The Journal of comparative neurology.

[11]  Thomas R. Gingeras,et al.  STAR: ultrafast universal RNA-seq aligner , 2013, Bioinform..

[12]  C. Liang,et al.  In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro , 2007, Nature Protocols.

[13]  T. Sejnowski,et al.  [Letters to nature] , 1996, Nature.

[14]  M. Marín‐padilla.  Structural abnormalities of the cerebral cortex in human chromosomal aberrations: a Golgi study. , 1972, Brain research.

[15]  D. Stout.  Stone toolmaking and the evolution of human culture and cognition , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[16]  G. V. Van Hoesen,et al.  Prefrontal cortex in humans and apes: a comparative study of area 10. , 2001, American journal of physical anthropology.

[17]  K. Tanigaki,et al.  Neuronal migration abnormalities and its possible implications for schizophrenia , 2015, Front. Neurosci..

[18]  Pietro Liò,et al.  The BioMart community portal: an innovative alternative to large, centralized data repositories , 2015, Nucleic Acids Res..

[19]  D. Stout,et al.  The Endocast of MH1, Australopithecus sediba , 2011, Science.

[20]  Maximilian Bayer.  Human Evolution Through Developmental Change , 2016 .

[21]  I. Kostović,et al.  Prenatal development of neurons in the human prefrontal cortex: I. A qualitative Golgi study , 1988, The Journal of comparative neurology.

[22]  H. Damasio,et al.  The brain and its main anatomical subdivisions in living hominoids using magnetic resonance imaging. , 2000, Journal of human evolution.

[23]  J. DeFelipe,et al.  The pyramidal neuron of the cerebral cortex: Morphological and chemical characteristics of the synaptic inputs , 1992, Progress in Neurobiology.

[24]  D. Prince,et al.  Burst generating and regular spiking layer 5 pyramidal neurons of rat neocortex have different morphological features , 1990, The Journal of comparative neurology.

[25]  M. Marín‐Padilla,et al.  Prenatal and early postnatal ontogenesis of the human motor cortex: a golgi study. I. The sequential development of the cortical layers. , 1970, Brain research.

[26]  P. Arlotta,et al.  Neuronal subtype specification in the cerebral cortex , 2007, Nature Reviews Neuroscience.

[27]  Ahmed Mahfouz,et al.  Visualizing the spatial gene expression organization in the brain through non-linear similarity embeddings. , 2015, Methods.

[28]  Gene W. Yeo,et al.  Differential LINE-1 regulation in pluripotent stem cells of humans and other great apes , 2013, Nature.

[29]  S. Pääbo,et al.  Intra- and Interspecific Variation in Primate Gene Expression Patterns , 2002, Science.

[30]  E. Vrba.  Multiphasic growth models and the evolution of prolonged growth exemplified by human brain evolution. , 1998, Journal of theoretical biology.

[31]  S. Pääbo,et al.  Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism , 2016, PLoS biology.

[32]  Erik Meijering,et al.  Methods for cell and particle tracking. , 2012, Methods in enzymology.

[33]  P. Hof,et al.  Developmental changes in the spatial organization of neurons in the neocortex of humans and common chimpanzees , 2013, The Journal of comparative neurology.

[34]  F. Gage,et al.  2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size , 2016, Cell stem cell.

[35]  B Hagberg,et al.  Rett syndrome: 3‐D confocal microscopy of cortical pyramidal dendrites and afferents , 1994, Neuroreport.

[36]  S. Leigh.  Brain growth, life history, and cognition in primate and human evolution , 2004, American journal of primatology.

[37]  C. Walsh,et al.  Molecular insights into human brain evolution , 2005, Nature.

[38]  P. Hof,et al.  Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans , 2013, Proceedings of the National Academy of Sciences.

[39]  S. Ambrose.  Paleolithic Technology and Human Evolution , 2001, Science.

[40]  R. Joyce,et al.  1 Mesoamerica : A Working Model for Archaeology , 2003 .

[41]  Kathleen Campbell,et al.  Cell cycle networks link gene expression dysregulation, mutation, and brain maldevelopment in autistic toddlers , 2015, Molecular systems biology.

[42]  N. Spruston.  Pyramidal neurons: dendritic structure and synaptic integration , 2008, Nature Reviews Neuroscience.

[43]  R. Nieuwenhuys.  The neocortex , 1994, Anatomy and Embryology.

[44]  K. Amunts,et al.  Spatial organization of neurons in the frontal pole sets humans apart from great apes. , 2011, Cerebral cortex.

[45]  K. Kaibuchi,et al.  Regulation of neuronal migration, an emerging topic in autism spectrum disorders , 2016, Journal of neurochemistry.

[46]  F. Gage,et al.  Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia , 2014, Molecular Psychiatry.

[47]  J. Hutsler,et al.  Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders , 2010, Brain Research.

[48]  H. Uylings,et al.  Biphasic dendritic growth of dorsolateral prefrontal cortex associative neurons and early cognitive development , 2018, Croatian medical journal.

[49]  Paul Theodor Pyl,et al.  HTSeq—a Python framework to work with high-throughput sequencing data , 2014, bioRxiv.

[50]  S. Pääbo,et al.  Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques. , 2012, Genome research.

[51]  Mark D. Robinson,et al.  edgeR: a Bioconductor package for differential expression analysis of digital gene expression data , 2009, Bioinform..

[52]  M. King,et al.  Evolution at two levels in humans and chimpanzees. , 1975, Science.

[53]  Gene W. Yeo,et al.  Differential L 1 regulation in pluripotent stem cells of humans and apes , 2013 .

[54]  Milos Judas,et al.  Lifespan alterations of basal dendritic trees of pyramidal neurons in the human prefrontal cortex: a layer-specific pattern. , 2008, Cerebral cortex.

[55]  Hua Su,et al.  MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors. , 2010, Cell stem cell.

[56]  Fred H. Gage,et al.  A Model for Neural Development and Treatment of Rett Syndrome Using Human Induced Pluripotent Stem Cells , 2010, Cell.

[57]  Nicole Barger,et al.  A comparative volumetric analysis of the amygdaloid complex and basolateral division in the human and ape brain. , 2007, American journal of physical anthropology.