The Cellular and Molecular Landscapes of the Developing Human Central Nervous System

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2016 Jan 23

PMID 26796689

Citations 353

Authors

John C Silbereis

Sirisha Pochareddy

Ying Zhu

Mingfeng Li

Nenad Sestan

Affiliations

Soon will be listed here.

Abstract

The human CNS follows a pattern of development typical of all mammals, but certain neurodevelopmental features are highly derived. Building the human CNS requires the precise orchestration and coordination of myriad molecular and cellular processes across a staggering array of cell types and over a long period of time. Dysregulation of these processes affects the structure and function of the CNS and can lead to neurological or psychiatric disorders. Recent technological advances and increased focus on human neurodevelopment have enabled a more comprehensive characterization of the human CNS and its development in both health and disease. The aim of this review is to highlight recent advancements in our understanding of the molecular and cellular landscapes of the developing human CNS, with focus on the cerebral neocortex, and the insights these findings provide into human neural evolution, function, and dysfunction.

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References

Workman A, Charvet C, Clancy B, Darlington R, Finlay B . Modeling transformations of neurodevelopmental sequences across mammalian species. J Neurosci. 2013; 33(17):7368-83. PMC: 3928428. DOI: 10.1523/JNEUROSCI.5746-12.2013. View

Cai X, Evrony G, Lehmann H, Elhosary P, Mehta B, Poduri A . Single-cell, genome-wide sequencing identifies clonal somatic copy-number variation in the human brain. Cell Rep. 2015; 10(4):645. DOI: 10.1016/j.celrep.2015.01.028. View

Gulyas A, Megias M, Emri Z, Freund T . Total number and ratio of excitatory and inhibitory synapses converging onto single interneurons of different types in the CA1 area of the rat hippocampus. J Neurosci. 1999; 19(22):10082-97. PMC: 6782984. View

Franchini L, Pollard K . Can a few non-coding mutations make a human brain?. Bioessays. 2015; 37(10):1054-61. PMC: 5054932. DOI: 10.1002/bies.201500049. View

Shibata M, Gulden F, Sestan N . From trans to cis: transcriptional regulatory networks in neocortical development. Trends Genet. 2015; 31(2):77-87. PMC: 4382006. DOI: 10.1016/j.tig.2014.12.004. View

Lindblad-Toh K, Garber M, Zuk O, Lin M, Parker B, Washietl S . A high-resolution map of human evolutionary constraint using 29 mammals. Nature. 2011; 478(7370):476-82. PMC: 3207357. DOI: 10.1038/nature10530. View

Amunts K, Schleicher A, Ditterich A, Zilles K . Broca's region: cytoarchitectonic asymmetry and developmental changes. J Comp Neurol. 2003; 465(1):72-89. DOI: 10.1002/cne.10829. View

Hu W, Chahrour M, Walsh C . The diverse genetic landscape of neurodevelopmental disorders. Annu Rev Genomics Hum Genet. 2014; 15:195-213. PMC: 10591257. DOI: 10.1146/annurev-genom-090413-025600. View

Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A . Integrative analysis of 111 reference human epigenomes. Nature. 2015; 518(7539):317-30. PMC: 4530010. DOI: 10.1038/nature14248. View

10.

Marner L, Nyengaard J, Tang Y, Pakkenberg B . Marked loss of myelinated nerve fibers in the human brain with age. J Comp Neurol. 2003; 462(2):144-52. DOI: 10.1002/cne.10714. View

11.

Ip B, Wappler I, Peters H, Lindsay S, Clowry G, Bayatti N . Investigating gradients of gene expression involved in early human cortical development. J Anat. 2010; 217(4):300-11. PMC: 2992409. DOI: 10.1111/j.1469-7580.2010.01259.x. View

12.

Bae B, Tietjen I, Atabay K, Evrony G, Johnson M, Asare E . Evolutionarily dynamic alternative splicing of GPR56 regulates regional cerebral cortical patterning. Science. 2014; 343(6172):764-8. PMC: 4480613. DOI: 10.1126/science.1244392. View

13.

Dehay C, Kennedy H, Kosik K . The outer subventricular zone and primate-specific cortical complexification. Neuron. 2015; 85(4):683-94. DOI: 10.1016/j.neuron.2014.12.060. View

14.

Chi J, Dooling E, Gilles F . Left-right asymmetries of the temporal speech areas of the human fetus. Arch Neurol. 1977; 34(6):346-8. DOI: 10.1001/archneur.1977.00500180040008. View

15.

Clowry G . The dependence of spinal cord development on corticospinal input and its significance in understanding and treating spastic cerebral palsy. Neurosci Biobehav Rev. 2007; 31(8):1114-24. DOI: 10.1016/j.neubiorev.2007.04.007. View

16.

Mazin P, Xiong J, Liu X, Yan Z, Zhang X, Li M . Widespread splicing changes in human brain development and aging. Mol Syst Biol. 2013; 9:633. PMC: 3564255. DOI: 10.1038/msb.2012.67. View

17.

Kang H, Kawasawa Y, Cheng F, Zhu Y, Xu X, Li M . Spatio-temporal transcriptome of the human brain. Nature. 2011; 478(7370):483-9. PMC: 3566780. DOI: 10.1038/nature10523. View

18.

Tay Y, Rinn J, Pandolfi P . The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483):344-52. PMC: 4113481. DOI: 10.1038/nature12986. View

19.

Catts V, Fung S, Long L, Joshi D, Vercammen A, Allen K . Rethinking schizophrenia in the context of normal neurodevelopment. Front Cell Neurosci. 2013; 7:60. PMC: 3654207. DOI: 10.3389/fncel.2013.00060. View

20.

Han K, Gennarino V, Lee Y, Pang K, Hashimoto-Torii K, Choufani S . Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p. Genes Dev. 2013; 27(5):485-90. PMC: 3605462. DOI: 10.1101/gad.207456.112. View