7q11.23 Syndromes Reveal BAZ1B as a Master Regulator of the Modern Human Face and Validate the Self-Domestication Hypothesis

Zanella, M.; Vitriolo, A.; Andirko, A.; Martins, P. T.; Sturm, S.; O'Rourke, T.; Laugsch, M.; Malerba, N.; Skaros, A.; Trattaro, S.; Germain, P.-L.; Merla, G.; Rada-Iglesias, A.; Boeckx, C.; Testa, G.

doi:10.1101/570036

bioRxiv · 10.1101/570036

7q11.23 Syndromes Reveal BAZ1B as a Master Regulator of the Modern Human Face and Validate the Self-Domestication Hypothesis

Zanella, M.·Vitriolo, A.·Andirko, A.·Martins, P. T.·Sturm, S.·O'Rourke, T.·Laugsch, M.·Malerba, N.·Skaros, A.·Trattaro, S.·Germain, P.-L.·Merla, G.·Rada-Iglesias, A.·Boeckx, C.·Testa, G.

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Abstract

Symmetrical 7q11.23 dosage alterations cause craniofacial and cognitive/behavioral phenotypes that provide a privileged entry point into the evolution of the modern human face and (pro-) sociality. We undertook a functional dissection of chromatin remodeler BAZ1B in neural crest stem cells (NCSCs) from a uniquely informative cohort of typical and atypical patients harboring 7q11.23 Copy Number Variants (CNVs). Our results reveal a key contribution of BAZ1B to NCSC in vitro induction and migration, coupled with a crucial involvement in neural crest (NC)-specific transcriptional circuits and distal regulation. By intersecting our experimental data with new paleogenetic analyses comparing modern and archaic humans, we uncover a modern-specific enrichment for regulatory changes both in BAZ1B and its experimentally defined downstream targets, thereby providing the first empirical validation of the self-domestication hypothesis and positioning BAZ1B as a master regulator of the modern human face.\n\nOne Sentence SummaryBAZ1B dosage shapes the modern human face.

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Zanella, M., Vitriolo, A., Andirko, A., Martins, P. T., Sturm, S., O'Rourke, T., Laugsch, M., Malerba, N., Skaros, A., Trattaro, S., Germain, P.-L., Merla, G., Rada-Iglesias, A., Boeckx, C., Testa, G.. 2019-03-06. 7q11.23 Syndromes Reveal BAZ1B as a Master Regulator of the Modern Human Face and Validate the Self-Domestication Hypothesis. https://doi.org/10.1101/570036

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