Matches in SemOpenAlex for { <https://semopenalex.org/work/W2891489034> ?p ?o ?g. }
- W2891489034 abstract "Abstract An intriguing question in medical biology is how mutations in functionally distinct genes can lead to similar clinical phenotypes. For example, patients with mutations in distinct epigenetic regulators EHMT1, MBD5, MLL3 or SMARCB1 share the core clinical features of intellectual disability (ID), autism spectrum disorder (ASD) and facial dysmorphisms. To elucidate how these phenotypic similarities are reflected by convergence at the molecular, cellular and neuronal network level, we directly compared the effects of their loss of function in neurons. Interestingly, knockdown of each gene resulted in hyperactive neuronal networks with altered patterns of synchronized activity. At the single-cell level, we found genotype-specific changes in intrinsic excitability and excitatory-inhibitory balance, but in all cases leading to increased excitability. Congruent with our physiological findings, we identified dysregulated genes that converge on biological and cellular pathways related to neuronal excitability and synaptic function, including genes previously implicated in ID/ASD. Yet, our data suggests that the common cellular phenotypes depend on the ensemble of dysregulated genes engaged in neuronal excitability rather than the direction of transcriptional changes of individual genes. The demonstration of increasing convergence from molecular pathways to neuronal networks may be a paradigm for other types of ID/ASD." @default.
- W2891489034 created "2018-09-27" @default.
- W2891489034 creator A5000602972 @default.
- W2891489034 creator A5003992877 @default.
- W2891489034 creator A5010917186 @default.
- W2891489034 creator A5018326193 @default.
- W2891489034 creator A5021629516 @default.
- W2891489034 creator A5027471359 @default.
- W2891489034 creator A5028012901 @default.
- W2891489034 creator A5032358298 @default.
- W2891489034 creator A5044288722 @default.
- W2891489034 creator A5056438582 @default.
- W2891489034 creator A5058126558 @default.
- W2891489034 creator A5073806066 @default.
- W2891489034 creator A5088625820 @default.
- W2891489034 creator A5089383129 @default.
- W2891489034 creator A5089695515 @default.
- W2891489034 creator A5091740728 @default.
- W2891489034 date "2018-09-05" @default.
- W2891489034 modified "2023-09-27" @default.
- W2891489034 title "Distinct pathogenic genes causing intellectual disability and autism exhibit overlapping effects on neuronal network development" @default.
- W2891489034 cites W1485428340 @default.
- W2891489034 cites W1496885962 @default.
- W2891489034 cites W1582868277 @default.
- W2891489034 cites W1613369435 @default.
- W2891489034 cites W1875202049 @default.
- W2891489034 cites W1900500057 @default.
- W2891489034 cites W1968916422 @default.
- W2891489034 cites W1984116678 @default.
- W2891489034 cites W1990284480 @default.
- W2891489034 cites W1995647101 @default.
- W2891489034 cites W2015416439 @default.
- W2891489034 cites W2018461674 @default.
- W2891489034 cites W2020702702 @default.
- W2891489034 cites W2022093187 @default.
- W2891489034 cites W2023195612 @default.
- W2891489034 cites W2037638076 @default.
- W2891489034 cites W2048447429 @default.
- W2891489034 cites W2064241002 @default.
- W2891489034 cites W2064609029 @default.
- W2891489034 cites W2069814630 @default.
- W2891489034 cites W2073567531 @default.
- W2891489034 cites W2075764106 @default.
- W2891489034 cites W2076040334 @default.
- W2891489034 cites W2078544102 @default.
- W2891489034 cites W2080301714 @default.
- W2891489034 cites W2080700771 @default.
- W2891489034 cites W2089360863 @default.
- W2891489034 cites W2090477486 @default.
- W2891489034 cites W2100663971 @default.
- W2891489034 cites W2117787632 @default.
- W2891489034 cites W2118745131 @default.
- W2891489034 cites W2121444603 @default.
- W2891489034 cites W2121484182 @default.
- W2891489034 cites W2128016314 @default.
- W2891489034 cites W2129032286 @default.
- W2891489034 cites W2130350241 @default.
- W2891489034 cites W2133465414 @default.
- W2891489034 cites W2134256373 @default.
- W2891489034 cites W2152902515 @default.
- W2891489034 cites W2163771097 @default.
- W2891489034 cites W2169456326 @default.
- W2891489034 cites W2179438025 @default.
- W2891489034 cites W2229627499 @default.
- W2891489034 cites W2298642101 @default.
- W2891489034 cites W2337092408 @default.
- W2891489034 cites W2360045337 @default.
- W2891489034 cites W2472342174 @default.
- W2891489034 cites W2510223785 @default.
- W2891489034 cites W2537142116 @default.
- W2891489034 cites W2568529112 @default.
- W2891489034 cites W2570036960 @default.
- W2891489034 cites W2590330613 @default.
- W2891489034 cites W2668293001 @default.
- W2891489034 cites W2745586800 @default.
- W2891489034 cites W2760462427 @default.
- W2891489034 cites W2766489743 @default.
- W2891489034 cites W2782325897 @default.
- W2891489034 cites W2783641147 @default.
- W2891489034 cites W2783726586 @default.
- W2891489034 cites W2951406042 @default.
- W2891489034 doi "https://doi.org/10.1101/408252" @default.
- W2891489034 hasPublicationYear "2018" @default.
- W2891489034 type Work @default.
- W2891489034 sameAs 2891489034 @default.
- W2891489034 citedByCount "1" @default.
- W2891489034 countsByYear W28914890342019 @default.
- W2891489034 crossrefType "posted-content" @default.
- W2891489034 hasAuthorship W2891489034A5000602972 @default.
- W2891489034 hasAuthorship W2891489034A5003992877 @default.
- W2891489034 hasAuthorship W2891489034A5010917186 @default.
- W2891489034 hasAuthorship W2891489034A5018326193 @default.
- W2891489034 hasAuthorship W2891489034A5021629516 @default.
- W2891489034 hasAuthorship W2891489034A5027471359 @default.
- W2891489034 hasAuthorship W2891489034A5028012901 @default.
- W2891489034 hasAuthorship W2891489034A5032358298 @default.
- W2891489034 hasAuthorship W2891489034A5044288722 @default.
- W2891489034 hasAuthorship W2891489034A5056438582 @default.
- W2891489034 hasAuthorship W2891489034A5058126558 @default.
- W2891489034 hasAuthorship W2891489034A5073806066 @default.