Products & Services


Nanopore sequencing offers advantages in all areas of research. Our offering includes DNA sequencing, as well as RNA and gene expression analysis and future technology for analysing proteins.

Learn about applications
View all Applications
News Explore

Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis


Date: 31st May 2018 | Source: Cell

Authors: Ian T Fiddes, Gerrald A Lodewijk, Meghan M Mooring, Colleen M Bosworth, Adam D Ewing, Gary L Mantalas, Adam M Novak, Anouk van den Bout, Alex Bishara, Jimi L Rosenkrantz, Ryan Lorig-Roach, Andrew R Field, Maximillian Haeussler, Lotte Russo, Aparna Bhaduri, Tomasz J Nowakowski, Alex A Pollen, Max L Dougherty, Xander Nuttle, Marie-Claude Addor, Simon Zwolinski, Sol Katzman, Arnold Kreigstein, Evan E Eichler, Sofie R Salama, Frank MJ Jacobs, David Haussler.

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 that three paralogs of human-specific NOTCH2NL are highly expressed in radial glia. Functional analysis reveals that 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.

Read the full text

Recommended for you

Open a chat to talk to our sales team