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RNA-seq to investigate how human-specific Notch2 paralogs expand cortical neurogenesis through regulation of Delta/Notch interactions.

ABSTRACT: The human cerebral cortex underwent rapid enlargement and complexification during recent evolution. Hominid-specific (HS) genes arising from genomic duplications may be involved, but it remains unclear how much and which HS genes contribute to human brain development. Using tailored RNAseq profiling, we identify a repertoire of >60 HS genes that display robust and dynamic expression during human fetal corticogenesis. Among these, Notch2NL genes stood out as human-specific Notch2 paralogs that promotes cortical progenitor maintenance. Clonal analyses of human cortical progenitors revealed that Notch2NL promotes their expansion by increasing self-renewal, ultimately leading to higher clonal neuronal output. Notch2NL acts by direct activation of the Notch pathway, through cell-autonomous inhibition of Delta/Notch interactions. Our data identify a large repertoire of newly evolved genes linking human brain development and evolution, and indicate how human-specific Notch paralogs may have contributed to the expansion of the human brain.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Homo sapiens

SUBMITTER: Vincent Detours

PROVIDER: E-MTAB-6232 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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