Transcriptional Dysregulation of Neocortical Circuit Assembly in ASD

Overview

Journal Int Rev Neurobiol

Specialties Biology
Neurology
Psychiatry

Date 2013 Dec 3

PMID 24290386

Citations 22

Authors

Kenneth Y Kwan

Affiliations

Soon will be listed here.

Abstract

Autism spectrum disorders (ASDs) impair social cognition and communication, key higher-order functions centered in the human neocortex. The assembly of neocortical circuitry is a precisely regulated developmental process susceptible to genetic alterations that can ultimately affect cognitive abilities. Because ASD is an early onset neurodevelopmental disorder that disrupts functions executed by the neocortex, miswiring of neocortical circuits has been hypothesized to be an underlying mechanism of ASD. This possibility is supported by emerging genetic findings and data from imaging studies. Recent research on neocortical development has identified transcription factors as key determinants of neocortical circuit assembly, mediating diverse processes including neuronal specification, migration, and wiring. Many of these TFs (TBR1, SOX5, FEZF2, and SATB2) have been implicated in ASD. Here, I will discuss the functional roles of these transcriptional programs in neocortical circuit development and their neurobiological implications for the emerging etiology of ASD.

Citing Articles

The chromatin remodeler ADNP regulates neurodevelopmental disorder risk genes and neocortical neurogenesis.

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Rare predicted deleterious FEZF2 variants are associated with a neurodevelopmental phenotype.

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References

De Carlos J, OLeary D . Growth and targeting of subplate axons and establishment of major cortical pathways. J Neurosci. 1992; 12(4):1194-211. PMC: 6575791. View

Tarabykin V, Stoykova A, Usman N, Gruss P . Cortical upper layer neurons derive from the subventricular zone as indicated by Svet1 gene expression. Development. 2001; 128(11):1983-93. DOI: 10.1242/dev.128.11.1983. View

ORoak B, Vives L, Girirajan S, Karakoc E, Krumm N, Coe B . Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature. 2012; 485(7397):246-50. PMC: 3350576. DOI: 10.1038/nature10989. View

Nadarajah B, Parnavelas J . Modes of neuronal migration in the developing cerebral cortex. Nat Rev Neurosci. 2002; 3(6):423-32. DOI: 10.1038/nrn845. View

Marin-Padilla M . Dual origin of the mammalian neocortex and evolution of the cortical plate. Anat Embryol (Berl). 1978; 152(2):109-26. DOI: 10.1007/BF00315920. View

de Rouvroit C, Goffinet A . A new view of early cortical development. Biochem Pharmacol. 1998; 56(11):1403-9. DOI: 10.1016/s0006-2952(98)00209-3. View

Molliver M, Kostovic I, Van Der Loos H . The development of synapses in cerebral cortex of the human fetus. Brain Res. 1973; 50(2):403-7. DOI: 10.1016/0006-8993(73)90741-5. View

Jones E . Neurotransmitters in the cerebral cortex. J Neurosurg. 1986; 65(2):135-53. DOI: 10.3171/jns.1986.65.2.0135. View

Shim S, Kwan K, Li M, Lefebvre V, Sestan N . Cis-regulatory control of corticospinal system development and evolution. Nature. 2012; 486(7401):74-9. PMC: 3375921. DOI: 10.1038/nature11094. View

10.

Shukla D, Keehn B, Lincoln A, Muller R . White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study. J Am Acad Child Adolesc Psychiatry. 2010; 49(12):1269-78, 1278.e1-2. PMC: 3346956. DOI: 10.1016/j.jaac.2010.08.018. View

11.

Neale B, Kou Y, Liu L, Maayan A, Samocha K, Sabo A . Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. 2012; 485(7397):242-5. PMC: 3613847. DOI: 10.1038/nature11011. View

12.

Haubensak W, Attardo A, Denk W, Huttner W . Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc Natl Acad Sci U S A. 2004; 101(9):3196-201. PMC: 365766. DOI: 10.1073/pnas.0308600100. View

13.

Skaar D, Shao Y, Haines J, Stenger J, Jaworski J, Martin E . Analysis of the RELN gene as a genetic risk factor for autism. Mol Psychiatry. 2004; 10(6):563-71. DOI: 10.1038/sj.mp.4001614. View

14.

Sessa A, Mao C, Colasante G, Nini A, Klein W, Broccoli V . Tbr2-positive intermediate (basal) neuronal progenitors safeguard cerebral cortex expansion by controlling amplification of pallial glutamatergic neurons and attraction of subpallial GABAergic interneurons. Genes Dev. 2010; 24(16):1816-26. PMC: 2922508. DOI: 10.1101/gad.575410. View

15.

Nagae L, Zarnow D, Blaskey L, Dell J, Khan S, Qasmieh S . Elevated mean diffusivity in the left hemisphere superior longitudinal fasciculus in autism spectrum disorders increases with more profound language impairment. AJNR Am J Neuroradiol. 2012; 33(9):1720-5. PMC: 7964775. DOI: 10.3174/ajnr.A3037. View

16.

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

17.

Konopka G, Friedrich T, Davis-Turak J, Winden K, Oldham M, Gao F . Human-specific transcriptional networks in the brain. Neuron. 2012; 75(4):601-17. PMC: 3645834. DOI: 10.1016/j.neuron.2012.05.034. View

18.

Lefebvre V, Dumitriu B, Penzo-Mendez A, Han Y, Pallavi B . Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors. Int J Biochem Cell Biol. 2007; 39(12):2195-214. PMC: 2080623. DOI: 10.1016/j.biocel.2007.05.019. View

19.

Caviness Jr V, Takahashi T, Nowakowski R . Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model. Trends Neurosci. 1995; 18(9):379-83. DOI: 10.1016/0166-2236(95)93933-o. View

20.

Fischbach G, Lord C . The Simons Simplex Collection: a resource for identification of autism genetic risk factors. Neuron. 2010; 68(2):192-5. DOI: 10.1016/j.neuron.2010.10.006. View