Dear Editor,The mammalian cerebral cortex,responsible for all higherorder brain functions,is organized into six layers of neurons that form distinct projections and connections within and outside the cortex.During cor...Dear Editor,The mammalian cerebral cortex,responsible for all higherorder brain functions,is organized into six layers of neurons that form distinct projections and connections within and outside the cortex.During cortical development,neural progenitor cells(NPCs)in the proliferative ventricular zone(VZ)and subventricular zone(SVZ)of the dorsal telencephalon produce projection neurons that migrate toward the pial surface to form the cortical plate(CP).展开更多
Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mechanisms remain largely unknown.Reproducible animal models mirroring...Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mechanisms remain largely unknown.Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited.Here,we describe a new mouse model of congenital hydrocephalus through knockout ofβ-catenin in Nkx2.1-expressing regional neural progenitors.Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood.Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis afterβ-catenin knockout.Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages.Thus,knockout ofβ-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.展开更多
基金supported by the National Natural Science Foundation of China (31371093 and 31671068)the Tsinghua Center for Life Sciences, and Tongji Hospital and School of Life Sciences and Technology, Tongji University, China
文摘Dear Editor,The mammalian cerebral cortex,responsible for all higherorder brain functions,is organized into six layers of neurons that form distinct projections and connections within and outside the cortex.During cortical development,neural progenitor cells(NPCs)in the proliferative ventricular zone(VZ)and subventricular zone(SVZ)of the dorsal telencephalon produce projection neurons that migrate toward the pial surface to form the cortical plate(CP).
基金This work was supported by grants from the National Key Research and Development Program of China(2018YFA0108000 and 2019YFA0110300)the National Natural Science Foundation of China(8205020,32000689,31400934,31771132,31872760,31801204,and 31800858)+3 种基金the Science and Technology Commission of Shanghai Municipality(19JC1415100 and 21140902300)the Shanghai Municipal Education Commission(C120114)China Postdoctoral Science Foundation(2017M621526)the Fundamental Research Funds for the Central Universities,and the Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(Stem Cell Strategic Biobank and Clinical Translation Platform of Stem Cell Technology,ZJ2018-ZD-004).
文摘Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mechanisms remain largely unknown.Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited.Here,we describe a new mouse model of congenital hydrocephalus through knockout ofβ-catenin in Nkx2.1-expressing regional neural progenitors.Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood.Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis afterβ-catenin knockout.Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages.Thus,knockout ofβ-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.
