Cornelia de Lange Syndrome (CdLS), which is reported to affect about 1 in 10,000 to 30,000 newborns, is a multisystem organ developmental disorder with relatively mild to severe effects. Among others, intellectual disability represents an important feature of this condition.Cornelia de Lange syndrome can result from mutations in at least five genes: NIPBL (nipped-B-like protein), SMC1A (structural maintenance of chromosomes 1A), SMC3 (structural maintenance of chromosomes 3), RAD21 (RAD21 Cohesin Complex Component), and HDAC8 (Histone deacetylase 8). It is believed that mutations in these genes cause CdLS by impairing the function of the cohesin complex (to which all the aforementioned genes contribute to the structure or function), disrupting gene regulation during critical stages of early development.Since intellectual disorder might result from alterations in neural development, in this work, we studied the role of Hdac8 gene in mouse neural stem cells and in vertebrate (D.rerio) brain development by knock-down and chemical inhibition experiments. An underlying features of Hdac8 deficiency is an increased cell death in the developing neural tissues, either in mouse NSCs and in zebrafish embryos.

Modeling Cornelia de Lange Syndrome in vitro and in vivo reveals a role for cohesin complex in neuronal survival and differentiation / D. Bottai, M. Spreafico, A.S. Pistocchi, G. Fazio, R. Adami, P. Grazioli, A. Canu, C. Bragato, S. Rigamonti, C. Parodi, G. Cazzaniga, A. Biondi, F. Cotelli, A. Selicorni, V. Massa. - In: HUMAN MOLECULAR GENETICS. - ISSN 0964-6906. - 28:1(2019 Jan), pp. 64-73.

Modeling Cornelia de Lange Syndrome in vitro and in vivo reveals a role for cohesin complex in neuronal survival and differentiation

Daniele Bottai;Marco Spreafico;Anna Pistocchi;Raffaella Adami;Paolo Grazioli;Adriana Canu;Silvia Rigamonti;Chiara Parodi;Franco Cotelli;Valentina Massa
2019-01

Abstract

Cornelia de Lange Syndrome (CdLS), which is reported to affect about 1 in 10,000 to 30,000 newborns, is a multisystem organ developmental disorder with relatively mild to severe effects. Among others, intellectual disability represents an important feature of this condition.Cornelia de Lange syndrome can result from mutations in at least five genes: NIPBL (nipped-B-like protein), SMC1A (structural maintenance of chromosomes 1A), SMC3 (structural maintenance of chromosomes 3), RAD21 (RAD21 Cohesin Complex Component), and HDAC8 (Histone deacetylase 8). It is believed that mutations in these genes cause CdLS by impairing the function of the cohesin complex (to which all the aforementioned genes contribute to the structure or function), disrupting gene regulation during critical stages of early development.Since intellectual disorder might result from alterations in neural development, in this work, we studied the role of Hdac8 gene in mouse neural stem cells and in vertebrate (D.rerio) brain development by knock-down and chemical inhibition experiments. An underlying features of Hdac8 deficiency is an increased cell death in the developing neural tissues, either in mouse NSCs and in zebrafish embryos.
mutation cell death; chromosomes; de lange syndrome; developmental disabilities; embryo gene expression; regulation genes; histone deacetylase; newborn intellectual disability; nerve tissue; vertebrates; zebrafish; mice; neural development; brain development; neural stem cells
Settore BIO/13 - Biologia Applicata
Settore BIO/14 - Farmacologia
Settore BIO/11 - Biologia Molecolare
Settore BIO/09 - Fisiologia
Settore BIO/18 - Genetica
14-set-2018
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/596446
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