Evolutionarily dynamic alternative splicing of GPR56 Regulates regional cerebral cortical patterning

Byoung Il Bae, Ian Tietjen, Kutay D. Atabay, Gilad D. Evrony, Matthew B. Johnson, Ebenezer Asare, Peter P. Wang, Ayako Y. Murayama, Kiho Im, Steven N. Lisgo, Lynne Overman, Nenad Sěstan, Bernard S. Chang, A. James Barkovich, P. Ellen Grant, Meral Topcu̧, Jeffrey Politsky, Hideyuki Okano, Xianhua Piao, Christopher A. Walsh

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

The human neocortex has numerous specialized functional areas whose formation is poorly understood. Here, we describe a 15-base pair deletion mutation in a regulatory element of GPR56 that selectively disrupts human cortex surrounding the Sylvian fissure bilaterally including "Broca's area," the primary language area, by disrupting regional GPR56 expression and blocking RFX transcription factor binding. GPR56 encodes a heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor required for normal cortical development and is expressed in cortical progenitor cells. GPR56 expression levels regulate progenitor proliferation. GPR56 splice forms are highly variable between mice and humans, and the regulatory element of gyrencephalic mammals directs restricted lateral cortical expression. Our data reveal a mechanism by which control of GPR56 expression pattern by multiple alternative promoters can influence stem cell proliferation, gyral patterning, and, potentially, neocortex evolution.

Original languageEnglish (US)
Pages (from-to)764-768
Number of pages5
JournalScience
Volume343
Issue number6172
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Alternative Splicing
Neocortex
Stem Cells
Guanine Nucleotides
Sequence Deletion
G-Protein-Coupled Receptors
Base Pairing
Mammals
Carrier Proteins
Language
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • General

Cite this

Bae, B. I., Tietjen, I., Atabay, K. D., Evrony, G. D., Johnson, M. B., Asare, E., ... Walsh, C. A. (2014). Evolutionarily dynamic alternative splicing of GPR56 Regulates regional cerebral cortical patterning. Science, 343(6172), 764-768. https://doi.org/10.1126/science.1244392
Bae, Byoung Il ; Tietjen, Ian ; Atabay, Kutay D. ; Evrony, Gilad D. ; Johnson, Matthew B. ; Asare, Ebenezer ; Wang, Peter P. ; Murayama, Ayako Y. ; Im, Kiho ; Lisgo, Steven N. ; Overman, Lynne ; Sěstan, Nenad ; Chang, Bernard S. ; Barkovich, A. James ; Grant, P. Ellen ; Topcu̧, Meral ; Politsky, Jeffrey ; Okano, Hideyuki ; Piao, Xianhua ; Walsh, Christopher A. / Evolutionarily dynamic alternative splicing of GPR56 Regulates regional cerebral cortical patterning. In: Science. 2014 ; Vol. 343, No. 6172. pp. 764-768.
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Bae, BI, Tietjen, I, Atabay, KD, Evrony, GD, Johnson, MB, Asare, E, Wang, PP, Murayama, AY, Im, K, Lisgo, SN, Overman, L, Sěstan, N, Chang, BS, Barkovich, AJ, Grant, PE, Topcu̧, M, Politsky, J, Okano, H, Piao, X & Walsh, CA 2014, 'Evolutionarily dynamic alternative splicing of GPR56 Regulates regional cerebral cortical patterning', Science, vol. 343, no. 6172, pp. 764-768. https://doi.org/10.1126/science.1244392

Evolutionarily dynamic alternative splicing of GPR56 Regulates regional cerebral cortical patterning. / Bae, Byoung Il; Tietjen, Ian; Atabay, Kutay D.; Evrony, Gilad D.; Johnson, Matthew B.; Asare, Ebenezer; Wang, Peter P.; Murayama, Ayako Y.; Im, Kiho; Lisgo, Steven N.; Overman, Lynne; Sěstan, Nenad; Chang, Bernard S.; Barkovich, A. James; Grant, P. Ellen; Topcu̧, Meral; Politsky, Jeffrey; Okano, Hideyuki; Piao, Xianhua; Walsh, Christopher A.

In: Science, Vol. 343, No. 6172, 01.01.2014, p. 764-768.

Research output: Contribution to journalArticle

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T1 - Evolutionarily dynamic alternative splicing of GPR56 Regulates regional cerebral cortical patterning

AU - Bae, Byoung Il

AU - Tietjen, Ian

AU - Atabay, Kutay D.

AU - Evrony, Gilad D.

AU - Johnson, Matthew B.

AU - Asare, Ebenezer

AU - Wang, Peter P.

AU - Murayama, Ayako Y.

AU - Im, Kiho

AU - Lisgo, Steven N.

AU - Overman, Lynne

AU - Sěstan, Nenad

AU - Chang, Bernard S.

AU - Barkovich, A. James

AU - Grant, P. Ellen

AU - Topcu̧, Meral

AU - Politsky, Jeffrey

AU - Okano, Hideyuki

AU - Piao, Xianhua

AU - Walsh, Christopher A.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - The human neocortex has numerous specialized functional areas whose formation is poorly understood. Here, we describe a 15-base pair deletion mutation in a regulatory element of GPR56 that selectively disrupts human cortex surrounding the Sylvian fissure bilaterally including "Broca's area," the primary language area, by disrupting regional GPR56 expression and blocking RFX transcription factor binding. GPR56 encodes a heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor required for normal cortical development and is expressed in cortical progenitor cells. GPR56 expression levels regulate progenitor proliferation. GPR56 splice forms are highly variable between mice and humans, and the regulatory element of gyrencephalic mammals directs restricted lateral cortical expression. Our data reveal a mechanism by which control of GPR56 expression pattern by multiple alternative promoters can influence stem cell proliferation, gyral patterning, and, potentially, neocortex evolution.

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U2 - 10.1126/science.1244392

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Bae BI, Tietjen I, Atabay KD, Evrony GD, Johnson MB, Asare E et al. Evolutionarily dynamic alternative splicing of GPR56 Regulates regional cerebral cortical patterning. Science. 2014 Jan 1;343(6172):764-768. https://doi.org/10.1126/science.1244392