Project description:We used FlashTag, a method to pulse-label and isolate APs in the mouse neocortex with high temporal resolution, to fate-map neuronal progeny following heterochronic transplantation of APs into younger embryos. We find that unlike differentiated IPs, which lose the ability to generate deep layer neurons when transplanted into a younger host, APs are temporally uncommitted and become molecularly respecified to generate normally earlier-born neuron types. These results indicate that AP temporal identity progression occurs in the absence of detectable fate restriction and reveal that differentiation status, rather than embryonic age, is the core determinant of temporal plasticity in the mammalian neocortex.
Project description:Morphogenesis of many protozoans depends on a polarized establishment of cortical cytoskeleton possessing the subpellicular microtubules (SPMTs), which are apically nucleated and anchored by the apical polar ring (APR). In the malaria parasite Plasmodium, APR can be observed when a round zygote differentiates to a crescent motile ookinete for mosquito midgut infection. So far, the fine structure and molecular components of APR as well as the underlying mechanism of APR-mediated apical positioning of SPMTs are largely unknown. Here, we report that a previously undescribed MT-binding protein APR2 localizes at APR and associates directly with apical SPMTs throughout ookinete morphogenesis. We resolve an unprecedented APR structure composed of a top ring plus approximate 60 radiating spines, with each spine fitting with an individual SPMT. APR2 disruption impairs ookinete morphological development and gliding motility, leading to failure of mosquito transmission of Plasmodium. The APR2-deficient ookinetes display defective apical anchorage of APR and SPMT due to the impaired integrity of APR. Using proximity labeling with APR2 as bait, we obtain a Plasmodium ookinete APR proteome for the first time and validate 10 new APR proteins. Among the proteins, APRp2 and APRp4, directly interacting with APR2, also mediate the apical anchorage of SPMTs. This study sheds light on the molecular basis of APR in the organization of SPMTs essential for ookinete morphogenesis and mosquito transmission of Plasmodium.
Project description:gnp07_regeneome_transdifferenciation - microdissection - Study of the moleculars mecanism during transdifferenciation of Root ApicalMeristem to Shoot Apical Meristem - middle of growth permits to induce transdifferenciation of root apical meristem to shoot apical meristem
Project description:gnp07_regeneome_transdifferenciation - microdissection - Study of the moleculars mecanism during transdifferenciation of Root ApicalMeristem to Shoot Apical Meristem - middle of growth permits to induce transdifferenciation of root apical meristem to shoot apical meristem 6 dye-swap - time course
Project description:We show that Polycomb repressive complexes (PRCs) regulate lineage choice between neural and non-neural fates in the olfactory epithelium. Conditional loss of Polycomb repressive complex 2 perturbs lesion-induced neurogenesis and misexpression of lineage-specific transcription factors in multipotent olfactory globose basal cells.
Project description:We show that Polycomb repressive complexes (PRCs) regulate lineage choice between neural and non-neural fates in the olfactory epithelium. Conditional loss of Polycomb repressive complex 2 perturbs lesion-induced neurogenesis and misexpression of lineage-specific transcription factors in multipotent olfactory globose basal cells.
Project description:During cortical development neurons are generated sequentially from basal progenitors (BPs) which specifically express the transcription factor Tbr2. We used fluorescent-activaed cell sorting (FACS) to isolate BPs from Tbr2GFP knockin reporter mice (Arnold SJ et al. Genesis, 2009) at early (embryonic day, E13) and late (embryonic day, E16) stages of cortical neurogenesis and determined mRNA expression profiles using mouse mRNA microarray (Illumina MouseWG-6 v2). Comparison of E13 and E16 mRNA expression profiles allowed us to identify regulatory gene networks for maintaining stage specific homeostasis of BPs throughout neurogenesis. FACS isolated BPs at E13 and E16 mouse brain cortex were used for microarray analyses. Six biological replicates (embryonic cortex from three different litters) for E13 and five biological replicates (embryonic cortex from three different litters) for E16 were analysed.
Project description:The cerebral cortex contains layers of neurons sequentially generated by distinct lineage-related progenitors. At the onset of corticogenesis, the first-born progenitors are apical progenitors (APs) whose asymmetric division give birth directly to neurons. Later, they switch to indirect neurogenesis by generating intermediate progenitors (IPs), which give rise to projection neurons of all cortical layers. While a direct lineage relationship between APs and IPs has been established, the molecular mechanism that controls their transition remains elusive. Our data suggest that interfering with codon translation speed triggers endoplasmic reticulum stress and the unfolded protein response (UPR), further impairing the generation of IPs and leading to microcephaly. Moreover, we demonstrate that a progressive downregulation of UPR in cortical progenitors acts as physiological signal to amplify IPs and promotes indirect neurogenesis. Thus, our findings reveal a hitherto unrecognized contribution of UPR to cell fate acquisition during mammalian brain development. Ribosome profiling and RNA-Seq of forebrains from E14.5 mouse embryos from wild type animals and mutants carrying a conditional knockout of ELP3 in cortical progenitors