Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis.
Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis.
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DOI：
10.1016/j.cell.2018.03.051
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发表时间：
2018-05-31
期刊：
影响因子：
64.5
通讯作者：
Haussler D
中科院分区：
文献类型：
--
作者：
Fiddes IT;Lodewijk GA;Mooring M;Bosworth CM;Ewing AD;Mantalas GL;Novak AM;van den Bout A;Bishara A;Rosenkrantz JL;Lorig-Roach R;Field AR;Haeussler M;Russo L;Bhaduri A;Nowakowski TJ;Pollen AA;Dougherty ML;Nuttle X;Addor MC;Zwolinski S;Katzman S;Kriegstein A;Eichler EE;Salama SR;Jacobs FMJ;Haussler D
在人类进化过程中导致大脑大小扩大的基因变化仍然难以捉摸。Notch信号是放射状胶质干细胞增殖所必需的，也是哺乳动物大脑皮层神经元数量的决定因素。我们发现三个人类特有的NOTCH2NL在放射状胶质细胞中高表达。功能分析表明，NOTCH2NL的不同等位基因通过直接与Notch受体相互作用来增强Notch信号转导。NOTCH2NL的异位表达延缓了神经前体细胞的分化，而缺失则加速了向皮质神经元的分化，这与Notch信号转导中的作用一致。此外，NOTCH2NL基因提供了1q21.1末端缺失/重复综合征的断裂点，其中重复与巨头症和自闭症有关，缺失与小头畸形和精神分裂症有关。因此，人类特有的NOTCH2NL基因的出现可能有助于较大的人类新皮质的快速进化，同时伴随着1q21.1基因座基因组稳定性的丧失，并导致反复出现的神经发育障碍。人类特有的Notch类似物在放射状胶质细胞中表达，增强Notch信号转导并影响神经元分化。
Genetic changes causing brain size expansion in human evolution have remained elusive. Notch signaling is essential for radial glia stem cell proliferation and is a determinant of neuronal number in the mammalian cortex. We find three paralogs of human-specific NOTCH2NL are highly expressed in radial glia. Functional analysis reveals different alleles of NOTCH2NL have varying potencies to enhance Notch signaling by interacting directly with NOTCH receptors. Consistent with a role in Notch signaling, NOTCH2NL ectopic expression delays differentiation of neuronal progenitors, while deletion accelerates differentiation into cortical neurons. Furthermore, NOTCH2NL genes provide the breakpoints in 1q21.1 distal deletion/duplication syndrome, where duplications are associated with macrocephaly and autism, and deletions with microcephaly and schizophrenia. Thus, the emergence of human-specific NOTCH2NL genes may have contributed to the rapid evolution of the larger human neocortex accompanied by loss of genomic stability at the 1q21.1 locus and resulting recurrent neurodevelopmental disorders. Human-specific Notch paralogs are expressed in radial glia, enhance Notch signaling and impact neuronal differentiation.
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影响因子：
64.8
作者：
Lazaridis, Iosif;Patterson, Nick;Mittnik, Alissa;Renaud, Gabriel;Mallick, Swapan;Kirsanow, Karola;Sudmant, Peter H.;Schraiber, Joshua G.;Castellano, Sergi;Lipson, Mark;Berger, Bonnie;Economou, Christos;Bollongino, Ruth;Fu, Qiaomei;Bos, Kirsten I.;Nordenfelt, Susanne;Li, Heng;de Filippo, Cesare;Pruefer, Kay;Sawyer, Susanna;Posth, Cosimo;Haak, Wolfgang;Hallgren, Fredrik;Fornander, Elin;Rohland, Nadin;Delsate, Dominique;Francken, Michael;Guinet, Jean-Michel;Wahl, Joachim;Ayodo, George;Babiker, Hamza A.;Bailliet, Graciela;Balanovska, Elena;Balanovsky, Oleg;Barrantes, Ramiro;Bedoya, Gabriel;Ben-Ami, Haim;Bene, Judit;Berrada, Fouad;Bravi, Claudio M.;Brisighelli, Francesca;Busby, George B. J.;Cali, Francesco;Churnosov, Mikhail;Cole, David E. C.;Corach, Daniel;Damba, Larissa;van Driem, George;Dryomov, Stanislav;Dugoujon, Jean-Michel;Fedorova, Sardana A.;Romero, Irene Gallego;Gubina, Marina;Hammer, Michael;Henn, Brenna M.;Hervig, Tor;Hodoglugil, Ugur;Jha, Aashish R.;Karachanak-Yankova, Sena;Khusainova, Rita;Khusnutdinova, Elza;Kittles, Rick;Kivisild, Toomas;Klitz, William;Kucinskas, Vaidutis;Kushniarevich, Alena;Laredj, Leila;Litvinov, Sergey;Loukidis, Theologos;Mahley, Robert W.;Melegh, Bela;Metspalu, Ene;Molina, Julio;Mountain, Joanna;Nakkalajarvi, Klemetti;Nesheva, Desislava;Nyambo, Thomas;Osipova, Ludmila;Parik, Jueri;Platonov, Fedor;Posukh, Olga;Romano, Valentino;Rothhammer, Francisco;Rudan, Igor;Ruizbakiev, Ruslan;Sahakyan, Hovhannes;Sajantila, Antti;Salas, Antonio;Starikovskaya, Elena B.;Tarekegn, Ayele;Toncheva, Draga;Turdikulova, Shahlo;Uktveryte, Ingrida;Utevska, Olga;Vasquez, Rene;Villena, Mercedes;Voevoda, Mikhail;Winkler, Cheryl A.;Yepiskoposyan, Levon;Zalloua, Pierre;Zemunik, Tatijana;Cooper, Alan;Capelli, Cristian;Thomas, Mark G.;Ruiz-Linares, Andres;Tishkoff, Sarah A.;Singh, Lalji;Thangaraj, Kumarasamy;Villems, Richard;Comas, David;Sukernik, Rem;Metspalu, Mait;Meyer, Matthias;Eichler, Evan E.;Burger, Joachim;Slatkin, Montgomery;Paeaebo, Svante;Kelso, Janet;Reich, David;Krause, Johannes
通讯作者：
Krause, Johannes
SRGAP2 人类特异性旁系同源物对 SRGAP2 功能的抑制可在脊柱成熟过程中诱导幼态持续
影响因子：
64.5
作者：
Charrier C;Joshi K;Coutinho-Budd J;Kim JE;Lambert N;de Marchena J;Jin WL;Vanderhaeghen P;Ghosh A;Sassa T;Polleux F
通讯作者：
Polleux F
影响因子：
4
作者：
Dennis MY;Eichler EE
通讯作者：
Eichler EE
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1073/pnas.252624099
发表时间：
2002-12-24
影响因子：
11.1
作者：
Karlström, H;Beatus, P;Lundkvist, J
通讯作者：
Lundkvist, J