microRNAs （miRNAs） constitute a unique class of endogenous small non-coding RNAs that regulate gene expression post-transcriptionally. Studies over the past decade have uncovered a r^curring paradigm in which miRNAs...microRNAs （miRNAs） constitute a unique class of endogenous small non-coding RNAs that regulate gene expression post-transcriptionally. Studies over the past decade have uncovered a r^curring paradigm in which miRNAs are key regulators of cellular behavior under various physiological and pathological conditions. Most surprising is the recent observation that miRNAs have emerged as competent players in somatic cell reprogramming, suggesting an especially significant role for these small RNAs in cell fate settings. Here, we discuss the possible mechanisms underlying miRNA-mediated cell programming （i.e., the development and differentiation of embryonic stem cells） and reprogramming （i.e., turning somatic cells into pluripo- tent stem cells or other lineages）, and provide a ＂Helm＂ model of miRNAs in cell fate decision and conversion.展开更多
Brain-specific loss of a microtubule-binding protein collapsin response mediator protein-2(CRMP2)in the mouse recapitulates many schizophrenia-like behaviors of human patients,possibly resulting from associated develo...Brain-specific loss of a microtubule-binding protein collapsin response mediator protein-2(CRMP2)in the mouse recapitulates many schizophrenia-like behaviors of human patients,possibly resulting from associated developmental deficits in neuronal differentiation,path-finding,and synapse formation.However,it is still unclear how the Crmp2 loss affects neuronal circuit function and plasticity.By conducting in vivo and ex vivo electrophysiological recording in the mouse primary visual cortex(V1),we reveal that CRMP2 exerts a key regulation on the timing of postnatal critical period(CP)for experience-dependent circuit plasticity of sensory cortex.In the developing V1,the Crmp2 deficiency induces not only a delayed maturation of visual tuning functions but also a precocious CP for visual input-induced ocular dominance plasticity and its induction activity–coincident binocular inputs right after eye-opening.Mechanistically,the Crmp2 deficiency accelerates the maturation process of cortical inhibitory transmission and subsequently promotes an early emergence of balanced excitatory-inhibitory cortical circuits during the postnatal development.Moreover,the precocious CP plasticity results in deteriorated binocular depth perception in adulthood.Thus,these findings suggest that the Crmp2 deficiency dysregulates the timing of CP for experience-dependent refinement of circuit connections and further leads to impaired sensory perception in later life.展开更多
基金supported by the National Natural Science Foundation of China(31200593,31230042,81070589)the Guangdong Natural Science Foundation(S2011040001760)+1 种基金the Fundamental Research Funds for the Central Universities(13lgpy40)the National Basic Research Program of China(2011CB811300)
文摘microRNAs （miRNAs） constitute a unique class of endogenous small non-coding RNAs that regulate gene expression post-transcriptionally. Studies over the past decade have uncovered a r^curring paradigm in which miRNAs are key regulators of cellular behavior under various physiological and pathological conditions. Most surprising is the recent observation that miRNAs have emerged as competent players in somatic cell reprogramming, suggesting an especially significant role for these small RNAs in cell fate settings. Here, we discuss the possible mechanisms underlying miRNA-mediated cell programming （i.e., the development and differentiation of embryonic stem cells） and reprogramming （i.e., turning somatic cells into pluripo- tent stem cells or other lineages）, and provide a ＂Helm＂ model of miRNAs in cell fate decision and conversion.
基金the National Natural Science Foundation of China(32071025,31921002,and 31730108)the Beijing Municipal Science&Technology Commission(Z181100001518001)+1 种基金the Interdisciplinary Research Fund of Beijing Normal Universitythe Strategic Priority Research Program and Innovation Program of the Chinese Academy of Sciences(XDB32020100)。
文摘Brain-specific loss of a microtubule-binding protein collapsin response mediator protein-2(CRMP2)in the mouse recapitulates many schizophrenia-like behaviors of human patients,possibly resulting from associated developmental deficits in neuronal differentiation,path-finding,and synapse formation.However,it is still unclear how the Crmp2 loss affects neuronal circuit function and plasticity.By conducting in vivo and ex vivo electrophysiological recording in the mouse primary visual cortex(V1),we reveal that CRMP2 exerts a key regulation on the timing of postnatal critical period(CP)for experience-dependent circuit plasticity of sensory cortex.In the developing V1,the Crmp2 deficiency induces not only a delayed maturation of visual tuning functions but also a precocious CP for visual input-induced ocular dominance plasticity and its induction activity–coincident binocular inputs right after eye-opening.Mechanistically,the Crmp2 deficiency accelerates the maturation process of cortical inhibitory transmission and subsequently promotes an early emergence of balanced excitatory-inhibitory cortical circuits during the postnatal development.Moreover,the precocious CP plasticity results in deteriorated binocular depth perception in adulthood.Thus,these findings suggest that the Crmp2 deficiency dysregulates the timing of CP for experience-dependent refinement of circuit connections and further leads to impaired sensory perception in later life.
