{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:54:06Z","timestamp":1791136446071,"version":"4.1.0"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"47","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,11,20]]},"abstract":"\n Neurons within each layer in the mammalian cortex have stereotypic projections. Four genes\u2014\n Fezf2, Ctip2, Tbr1<\/jats:italic>\n , and\n Satb2<\/jats:italic>\n \u2014regulate these projection identities. These genes also interact with each other, and it is unclear how these interactions shape the final projection identity. Here we show, by generating double mutants of\n Fezf2, Ctip2<\/jats:italic>\n , and\n Satb2<\/jats:italic>\n , that cortical neurons deploy a complex genetic switch that uses mutual repression to produce subcortical or callosal projections. We discovered that\n Tbr1, EphA4<\/jats:italic>\n , and\n Unc5H3<\/jats:italic>\n are critical downstream targets of Satb2 in callosal fate specification. This represents a unique role for\n Tbr1<\/jats:italic>\n , implicated previously in specifying corticothalamic projections. We further show that Tbr1 expression is dually regulated by\n Satb2<\/jats:italic>\n and\n Ctip2<\/jats:italic>\n in layers 2\u20135. Finally, we show that\n Satb2<\/jats:italic>\n and\n Fezf2<\/jats:italic>\n regulate two disease-related genes,\n Auts2<\/jats:italic>\n (Autistic Susceptibility Gene2) and\n Bhlhb5<\/jats:italic>\n (mutated in Hereditary Spastic Paraplegia), providing a molecular handle to investigate circuit disorders in neurodevelopmental diseases.\n <\/jats:p>","DOI":"10.1073\/pnas.1216793109","type":"journal-article","created":{"date-parts":[[2012,11,10]],"date-time":"2012-11-10T20:45:46Z","timestamp":1352580346000},"page":"19071-19078","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":176,"title":["A network of genetic repression and derepression specifies projection fates in the developing neocortex"],"prefix":"10.1073","volume":"109","author":[{"given":"Karpagam","family":"Srinivasan","sequence":"first","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dino P.","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie K.","family":"Bateson","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergana","family":"Dobreva","sequence":"additional","affiliation":[{"name":"Max-Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Kohwi","sequence":"additional","affiliation":[{"name":"Lawrence Berkeley National Laboratory, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terumi","family":"Kohwi-Shigematsu","sequence":"additional","affiliation":[{"name":"Lawrence Berkeley National Laboratory, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Grosschedl","sequence":"additional","affiliation":[{"name":"Max-Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K.","family":"McConnell","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,11,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.12.036"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1993.1281"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2008.05.006"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002285107"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016723108"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10219"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4131-10.2011"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804918105"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.012"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.028"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508732102"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.08.006"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-23-10346.2002"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.08.030"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806791105"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.023"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00211-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gep.2009.11.005"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhq190"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2009.57"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.03.011"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3109\/00048674.2010.534069"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pscychresns.2010.09.008"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2010.12.002"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7610.2010.02342.x"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2010.07.006"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2010.11.024"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3162-05.2006"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81795-X"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.24.5063"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2576"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1216793109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T22:17:34Z","timestamp":1649801854000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1216793109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,9]]},"references-count":31,"journal-issue":{"issue":"47","published-print":{"date-parts":[[2012,11,20]]}},"alternative-id":["10.1073\/pnas.1216793109"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1216793109","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,9]]},"assertion":[{"value":"2012-11-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}