We undertook a functional dissection of chromatin remodeler BAZ1B in neural crest (NC) stem cells (NCSCs) from a uniquely informative cohort of typical and atypical patients harboring 7q11.23 copy number variants. Our results reveal a key contribution of BAZ1B to NCSC in vitro induction and migration, coupled with a crucial involvement in NC-specific transcriptional circuits and distal regulation. By intersecting our experimental data with new paleogenetic analyses comparing modern and archaic humans, we found a modern-specific enrichment for regulatory changes both in BAZ1B and its experimentally defined downstream targets, thereby providing the first empirical validation of the human self-domestication hypothesis and positioning BAZ1B as a master regulator of the modern human face. In so doing, we provide experimental evidence that the craniofacial and cognitive/behavioral phenotypes caused by alterations of the Williams-Beuren syndrome critical region can serve as a powerful entry point into the evolution of the modern human face and prosociality.

Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication / M. Zanella, A. Vitriolo, A. Andirko, P.T. Martins, S. Sturm, T. O'Rourke, M. Laugsch, N. Malerba, SKAROS ADRIANOS, S. Trattaro, P. Germain, MIHAILOVIC MARIJA, G. Merla, A. Rada-Iglesias, C. Boeckx, TESTA GIUSEPPE. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 5:12(2019 Dec 01). [10.1126/sciadv.aaw7908]

Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication

M. Zanella
Primo
;
A. Vitriolo
Secondo
;
A. Skaros;S. Trattaro;P. Germain;M. Mihailovic;G. Testa
Ultimo
2019

Abstract

We undertook a functional dissection of chromatin remodeler BAZ1B in neural crest (NC) stem cells (NCSCs) from a uniquely informative cohort of typical and atypical patients harboring 7q11.23 copy number variants. Our results reveal a key contribution of BAZ1B to NCSC in vitro induction and migration, coupled with a crucial involvement in NC-specific transcriptional circuits and distal regulation. By intersecting our experimental data with new paleogenetic analyses comparing modern and archaic humans, we found a modern-specific enrichment for regulatory changes both in BAZ1B and its experimentally defined downstream targets, thereby providing the first empirical validation of the human self-domestication hypothesis and positioning BAZ1B as a master regulator of the modern human face. In so doing, we provide experimental evidence that the craniofacial and cognitive/behavioral phenotypes caused by alterations of the Williams-Beuren syndrome critical region can serve as a powerful entry point into the evolution of the modern human face and prosociality.
Settore BIO/11 - Biologia Molecolare
Settore BIO/13 - Biologia Applicata
Settore BIO/18 - Genetica
Settore MED/03 - Genetica Medica
Settore MED/04 - Patologia Generale
Settore BIO/08 - Antropologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/699570
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