--- res: bibo_abstract: - De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Jasmin foaf_name: Morandell, Jasmin foaf_surname: Morandell foaf_workInfoHomepage: http://www.librecat.org/personId=4739D480-F248-11E8-B48F-1D18A9856A87 - foaf_Person: foaf_givenName: Lena A foaf_name: Schwarz, Lena A foaf_surname: Schwarz foaf_workInfoHomepage: http://www.librecat.org/personId=29A8453C-F248-11E8-B48F-1D18A9856A87 - foaf_Person: foaf_givenName: Bernadette foaf_name: Basilico, Bernadette foaf_surname: Basilico foaf_workInfoHomepage: http://www.librecat.org/personId=36035796-5ACA-11E9-A75E-7AF2E5697425 orcid: 0000-0003-1843-3173 - foaf_Person: foaf_givenName: Saren foaf_name: Tasciyan, Saren foaf_surname: Tasciyan foaf_workInfoHomepage: http://www.librecat.org/personId=4323B49C-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0003-1671-393X - foaf_Person: foaf_givenName: Armel foaf_name: Nicolas, Armel foaf_surname: Nicolas foaf_workInfoHomepage: http://www.librecat.org/personId=2A103192-F248-11E8-B48F-1D18A9856A87 - foaf_Person: foaf_givenName: Christoph M foaf_name: Sommer, Christoph M foaf_surname: Sommer foaf_workInfoHomepage: http://www.librecat.org/personId=4DF26D8C-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0003-1216-9105 - foaf_Person: foaf_givenName: Caroline foaf_name: Kreuzinger, Caroline foaf_surname: Kreuzinger foaf_workInfoHomepage: http://www.librecat.org/personId=382077BA-F248-11E8-B48F-1D18A9856A87 - foaf_Person: foaf_givenName: Lisa foaf_name: Knaus, Lisa foaf_surname: Knaus foaf_workInfoHomepage: http://www.librecat.org/personId=3B2ABCF4-F248-11E8-B48F-1D18A9856A87 - foaf_Person: foaf_givenName: Zoe foaf_name: Dobler, Zoe foaf_surname: Dobler foaf_workInfoHomepage: http://www.librecat.org/personId=D23090A2-9057-11EA-883A-A8396FC7A38F - foaf_Person: foaf_givenName: Emanuele foaf_name: Cacci, Emanuele foaf_surname: Cacci - foaf_Person: foaf_givenName: Johann G foaf_name: Danzl, Johann G foaf_surname: Danzl foaf_workInfoHomepage: http://www.librecat.org/personId=42EFD3B6-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0001-8559-3973 - foaf_Person: foaf_givenName: Gaia foaf_name: Novarino, Gaia foaf_surname: Novarino foaf_workInfoHomepage: http://www.librecat.org/personId=3E57A680-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-7673-7178 bibo_doi: '10.1101/2020.01.10.902064 ' dct_date: 2020^xs_gYear dct_language: eng dct_publisher: Cold Spring Harbor Laboratory@ dct_title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development@ ...