--- res: bibo_abstract: - "Background\r\nProper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology .\r\nMethods\r\nHere, in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild type cells concomitantly in vivo using immunofluorescent techniques.\r\nResults\r\nWe revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages. Limitations While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients.\r\nConclusions\r\n\uFEFFOur genetic approach revealed several cell autonomous requirements of Wdfy3 in neuronal development that could underly the pathogenic mechanisms of WDFY3-related ASD conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for Wdfy3 in regulating neuronal function and interconnectivity in postnatal life.@eng" bibo_authorlist: - foaf_Person: foaf_givenName: Zachary foaf_name: Schaaf, Zachary foaf_surname: Schaaf - foaf_Person: foaf_givenName: Lyvin foaf_name: Tat, Lyvin foaf_surname: Tat - foaf_Person: foaf_givenName: Noemi foaf_name: Cannizzaro, Noemi foaf_surname: Cannizzaro - foaf_Person: foaf_givenName: Ralph foaf_name: Green, Ralph foaf_surname: Green - foaf_Person: foaf_givenName: Thomas foaf_name: Rülicke, Thomas foaf_surname: Rülicke - foaf_Person: foaf_givenName: Simon foaf_name: Hippenmeyer, Simon foaf_surname: Hippenmeyer foaf_workInfoHomepage: http://www.librecat.org/personId=37B36620-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0003-2279-1061 - foaf_Person: foaf_givenName: K foaf_name: Zarbalis, K foaf_surname: Zarbalis bibo_doi: 10.21203/rs.3.rs-1316167/v1 dct_date: 2022^xs_gYear dct_isPartOf: - http://id.crossref.org/issn/2693-5015 dct_language: eng dct_publisher: Research Square@ dct_title: WDFY3 cell autonomously controls neuronal migration@ fabio_hasPubmedId: PPR454733 ...