Planar cell polarity pathway and development of the human visual cortex
Authors: Shin Jean , Ma Shaojie , Hofer Edith , Patel Yash , Roshchupkin Gennady V. , Sousa André M. , Jian Xueqiu , Gottesman Rebecca , Mosley Thomas H. , Fornage Myriam , Saba Yasaman , Pirpamer Lukas , Schmidt Reinhold , Schmidt Helena , Carrion-Castillo Amaia , Crivello Fabrice , Mazoyer Bernard , Bis Joshua C. , Li Shuo , Yang Qiong , Luciano Michelle , Karama Sherif , Lewis Lindsay , Bastin Mark , Harris Mathew A. , Wardlaw Joanna M. , Deary Ian E. , Scholz Markus , Loeffler Markus , Witte Veronica , Beyer Frauke , Villringer Arno , Armstrong Nicola J , Mather Karen A. , Ames David , Jiang Jiyang , Kwok John B , Schofield Peter R. , Thalamuthu Anbupalam , Trollor Julian N. , Wright Margaret J. , Brodaty Henry , Wen Wei , Sachdev Perminder S. , Terzikhan Natalie , Evans Tavia E. , Adams Hieab H.H.H. , Ikram M. Arfan , Frenzel Stefan , van der Auwera-Palitschka Sandra , Wittfeld Katharina , Bülow Robin , Grabe Hans Jörgen , Tzourio Christophe , Mishra Aniket , Maingault Sophie , Debette Stephanie , Gillespie Nathan A. , Franz Carol E. , Kremen William S. , Ding Linda , Jahanshad Neda ,   the ENIGMA Consortium, Sestan Nenad , Pausova Zdenka , Seshadri Sudha , Paus Tomas ,   for the neuroCHARGE Working Group, Grasby Katrina L. , Jahanshad Neda , Painter Jodie N. , Colodro-Conde Lucía , Bralten Janita , Hibar Derrek P. , Lind Penelope A. , Pizzagalli Fabrizio , Ching Christopher R.K. , McMahon Mary Agnes B. , Shatokhina Natalia , Zsembik Leo , Agartz Ingrid , Alhusaini Saud , Almeida Marcio A.A. , Alnæs Dag , Amlien Inge K. , Andersson Micael , Ard Tyler , Armstrong Nicola J. , Ashley-Koch Allison , Bernard Manon , Brouwer Rachel M. , Buimer Elizabeth E.L. , Bülow Robin , Bürger Christian , Cannon Dara M. , Chakravarty Mallasr , Chen Qiang , Cheung Joshua W. , Couvy-Duchesne Baptiste , Dale Anders M. , Dalvie Shareefa , de Araujo Tânia K. , de Zubicaray Greig I. , de Zwarte Sonja M.C. , Braber Anouk den , Doan Nhat Trung , Dohm Katharina , Ehrlich Stefan , Engelbrecht Hannah-Ruth , Erk Susanne , Fan Chun Chieh , Fedko Iryna O. , Foley Sonya F. , Ford Judith M. , Fukunaga Masaki , Garrett Melanie E. , Ge Tian , Giddaluru Sudheer , Goldman Aaron L. , Groenewold Nynke A. , Grotegerd Dominik , Gurholt Tiril P. , Gutman Boris A. , Hansell Narelle K. , Harris Mathew A. , Harrison Marc B. , Haswell Courtney C. , Hauser Michael , Heslenfeld Dirk J. , Hoehn David , Holleran Laurena , Hoogman Martine , Hottenga Jouke-Jan , Ikeda Masashi , Janowitz Deborah , Jansen Iris E. , Jia Tianye , Jockwitz Christiane , Kanai Ryota , Karama Sherif , Kasperaviciute Dalia , Kaufmann Tobias , Kelly Sinead , Kikuchi Masataka , Klein Marieke , Knapp Michael , Knodt Annchen R. , Krämer Bernd , Lancaster Thomas M. , Lee Phil H. , Lett Tristram A. , Lewis Lindsay B. , Lopes-Cendes Iscia , Luciano Michelle , Macciardi Fabio , Marquand Andre F. , Mathias Samuel R. , Melzer Tracy R. , Milaneschi Yuri , Mirza-Schreiber Nazanin , Moreira Jose C.V. , Mühleisen Thomas W. , Müller-Myhsok Bertram , Najt Pablo , Nakahara Soichiro , Nho Kwangsik , Olde Loohuis Loes M. , Orfanos Dimitri Papadopoulos , Pearson John F. , Pitcher Toni L. , Pütz Benno , Ragothaman Anjanibhargavi , Rashid Faisal M. , Redlich Ronny , Reinbold Céline S. , Repple Jonathan , Richard Geneviève , Riedel Brandalyn C. , Risacher Shannon L. , Rocha Cristiane S. , Mota Nina Roth , Salminen Lauren , Saremi Arvin , Saykin Andrew J. , Schlag Fenja , Schmaal Lianne , Schofield Peter R. , Secolin Rodrigo , Shapland Chin Yang , Shen Li , Shin Jean , Shumskaya Elena , Sønderby Ida E. , Sprooten Emma , Strike Lachlan T. , Tansey Katherine E. , Teumer Alexander , Thalamuthu Anbupalam , Thomopoulos Sophia I. , Tordesillas-Gutiérrez Diana , Turner Jessica A. , Uhlmann Anne , Vallerga Costanza Ludovica , van der Meer Dennis , van Donkelaar Marjolein M.J. , van Eijk Liza , van Erp Theo G.M. , van Haren Neeltje E.M. , van Rooij Daan , van Tol Marie-José , Veldink Jan H. , Verhoef Ellen , Walton Esther , Wang Yunpeng , Wardlaw Joanna M. , Wen Wei , Westlye Lars T. , Whelan Christopher D. , Witt Stephanie H. , Wittfeld Katharina , Wolf Christiane , Wolfers Thomas , Yasuda Clarissa L. , Zaremba Dario , Zhang Zuo , Zhu Alyssa H. , Zwiers Marcel P. , Artiges Eric , Assareh Amelia A. , Ayesa-Arriola Rosa , Belger Aysenil , Brandt Christine L. , Brown Gregory G. , Cichon Sven , Curran Joanne E. , Davies Gareth E. , Degenhardt Franziska , Dietsche Bruno , Djurovic Srdjan , Doherty Colin P. , Espiritu Ryan , Garijo Daniel , Gil Yolanda , Gowland Penny A. , Green Robert C. , Häusler Alexander N. , Heindel Walter , Ho Beng-Choon , Hoffmann Wolfgang U. , Holsboer Florian , Homuth Georg , Hosten Norbert , Jack Clifford R. , Jang MiHyun , Jansen Andreas , Kolskår Knut , Koops Sanne , Krug Axel , Lim Kelvin O. , Luykx Jurjen J. , Mathalon Daniel H. , Mather Karen A. , Mattay Venkata S. , Matthews Sarah , Van Son Jaqueline Mayoral , McEwen Sarah C. , Melle Ingrid , Morris Derek W. , Mueller Bryon A. , Nauck Matthias , Nordvik Jan E. , Nöthen Markus M. , O’Leary Daniel S. , Opel Nils , Martinot Marie - Laure Paillère , Pike G. Bruce , Preda Adrian , Quinlan Erin B. , Ratnakar Varun , Reppermund Simone , Steen Vidar M. , Torres Fábio R. , Veltman Dick J. , Voyvodic James T. , Whelan Robert , White Tonya , Yamamori Hidenaga , Alvim Marina K.M. , Ames David , Anderson Tim J. , Andreassen Ole A. , Arias-Vasquez Alejandro , Bastin Mark E. , Baune Bernhard T. , Blangero John , Boomsma Dorret I. , Brodaty Henry , Brunner Han G. , Buckner Randy L. , Buitelaar Jan K. , Bustillo Juan R. , Cahn Wiepke , Calhoun Vince , Caseras Xavier , Caspers Svenja , Cavalleri Gianpiero L. , Cendes Fernando , Corvin Aiden , Crespo-Facorro Benedicto , Dalrymple-Alford John C. , Dannlowski Udo , de Geus Eco J.C. , Deary Ian J. , Delanty Norman , Depondt Chantal , Desrivières Sylvane , Donohoe Gary , Espeseth Thomas , Fernández Guillén , Fisher Simon E. , Flor Herta , Forstner Andreas J. , Francks Clyde , Franke Barbara , Glahn David C. , Gollub Randy L. , Grabe Hans J. , Gruber Oliver , Håberg Asta K. , Hariri Ahmad R. , Hartman Catharina A. , Hashimoto Ryota , Heinz Andreas , Hillegers Manon H.J. , Hoekstra Pieter J. , Holmes Avram J. , Hong L. Elliot , Hopkins William D. , Hulshoff Pol Hilleke E. , Jernigan Terry L. , Jönsson Erik G. , Kahn René S. , Kennedy Martin A. , Kircher Tilo T.J. , Kochunov Peter , Kwok John B.J. , Le Hellard Stephanie , Martin Nicholas G. , Martinot Jean - Luc , McDonald Colm , McMahon Katie L. , Meyer-Lindenberg Andreas , Morey Rajendra A. , Nyberg Lars , Oosterlaan Jaap , Ophoff Roel A. , Paus Tomas , Pausova Zdenka , Penninx Brenda W.J.H. , Polderman Tinca J.C. , Posthuma Danielle , Rietschel Marcella , Roffman Joshua L. , Rowland Laura M. , Sachdev Perminder S. , Sämann Philipp G. , Schumann Gunter , Sim Kang , Sisodiya Sanjay M. , Smoller Jordan W. , Sommer Iris E. , St Pourcain Beate , Stein Dan J. , Toga Arthur W. , Trollor Julian N. , Van der Wee Nic J.A. , van’t Ent Dennis , Völzke Henry , Walter Henrik , Weber Bernd , Weinberger Daniel R. , Wright Margaret J. , Zhou Juan , Stein Jason L. , Thompson Paul M. , Medland Sarah E. 
Published: August 2018

The radial unit hypothesis provides a framework for global (proliferation) and regional (distribution) expansion of the primate cerebral cortex. Using principal component analysis (PCA), we have identified cortical regions with shared variance in their surface area and cortical thickness, respectively, segmented from magnetic resonance images obtained in 23,800 participants. We then carried out meta-analyses of genome-wide association studies of the first two principal components for each phenotype. For surface area (but not cortical thickness), we have detected strong associations between each of the components and single nucleotide polymorphisms in a number of gene loci. The first (global) component was associated mainly with loci on chromosome 17 (9.5e-32 ≤ p ≤ 2.8e-10), including those detected previously as linked with intracranial volume and/or general cognitive function. The second (regional) component captured shared variation in the surface area of the primary and adjacent secondary visual cortices and showed a robust association with polymorphisms in a locus on chromosome 14 containing Disheveled Associated Activator of Morphogenesis 1 (DAAM1; p=2.4e-34). DAAM1 is a key component in the planar-cell-polarity signaling pathway. In follow-up studies, we have focused on the latter finding and established that: (1) DAAM1 is highly expressed between 12th and 22nd post-conception weeks in the human cerebral cortex; (2) genes co-expressed with DAAM1 in the primary visual cortex are enriched in mitochondria-related pathways; and (3) volume of the lateral geniculate nucleus, which projects to regions of the visual cortex staining for cytochrome oxidase (a mitochondrial enzyme), correlates with the surface area of the visual cortex in major-allele homozygotes but not in carriers of the minor allele. Altogether, we speculate that, in concert with thalamocortical input to cortical subplate, DAAM1 enables migration of neurons to cytochrome-oxidase rich regions of the visual cortex, and, in turn, facilitates regional expansion of this set of cortical regions during development.