02478nas a2200457   4500000000100000008004100001260001400042100001800056700002400074700001900098700002400117700001800141700002100159700001800180700002300198700001700221700002400238700002100262700002000283700002500303700001600328700001900344700002500363700001900388700002100407700001800428700002300446700002000469700001600489700002200505700002000527700002000547700002200567700001900589245008300608856005800691300001800749490000800767520123100775022001402006       2018                            d  c2018-5-311 aIan T. Fiddes1 aGerrald A. Lodewijk1 aMeghan Mooring1 aColleen M. Bosworth1 aAdam D. Ewing1 aGary L. Mantalas1 aAdam M. Novak1 aAnouk van den Bout1 aAlex Bishara1 aJimi L. Rosenkrantz1 aRyan Lorig-Roach1 aAndrew R. Field1 aMaximilian Haeussler1 aLotte Russo1 aAparna Bhaduri1 aTomasz J. Nowakowski1 aAlex A. Pollen1 aMax L. Dougherty1 aXander Nuttle1 aMarie-Claude Addor1 aSimon Zwolinski1 aSol Katzman1 aArnold Kriegstein1 aEvan E. Eichler1 aSofie R. Salama1 aFrank M.J. Jacobs1 aDavid Haussler00aHuman-specific NOTCH2NL genes affect Notch signaling and cortical neurogenesis  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986104/  a1356-1369.e220 v1733 aGenetic 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.,  a0092-8674