QBI Seminar: 'Human-specific NOTCH2NL genes: Possible contributors to human's evolutionary increase in brain size'
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- Dr Frank Jacobs
University of Amsterdam, Swammerdam Institute for Life Sciences (SILS)
Science Park 904, The Netherlands
Title: 'Human-specific NOTCH2NL genes: Possible contributors to human's evolutionary increase in brain size'
Abstract: Genetic changes causing dramatic brain size expansion in human evolution have remained elusive. Notch signaling is essential for radial glia stem cell proliferation and a determinant of neuronal number in the mammalian cortex. In this talk, I will discuss our recent discoveries regarding a cluster of human-specific NOTCH-like genes called NOTCH2NL. NOTCH2NL genes emerged in the human genome as a result of a complex series of genomic structural rearrangements, with the last ones marking the birth of NOTCH2NL genes between 4 and 0.5 million years. 2 paralogs of NOTCH2NL are highly expressed in ventricular and outer radial glia cells of the fetal human brain and have varying potencies to influence Notch signaling. Genetic deletion of NOTCH2NL genes in human cortical organoids, as well as the association of the NOTCH2NL locus to brain size abnormalities suggests an important role for NOTCH2NL genes during normal human cortical development in vivo. These discoveries suggest that the creation of NOTCH2NL genes during human evolution may have contributed to the rapid evolution of the larger hominin neocortex, but ironically, this happened at the expense of genomic instability where NOTCH2NL genes were born.
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