2 research outputs found
Dynamic interplay between thalamic activity and Cajal-Retzius cells regulates the wiring of cortical layer 1
Cortical wiring relies on guidepost cells and activity-dependent processes that are thought to act sequentially. Here, we show that the construction of layer 1 (L1), a main site of top-down integration, is regulated by crosstalk between transient Cajal-Retzius cells (CRc) and spontaneous activity of the thalamus, a main driver of bottom-up information. While activity was known to regulate CRc migration and elimination, we found that prenatal spontaneous thalamic activity and NMDA receptors selectively control CRc early density, without affecting their demise. CRc density, in turn, regulates the distribution of upper layer interneurons and excitatory synapses, thereby drastically impairing the apical dendrite activity of output pyramidal neurons. In contrast, postnatal sensory-evoked activity had a limited impact on L1 and selectively perturbed basal dendrites synaptogenesis. Collectively, our study highlights a remarkable interplay between thalamic activity and CRc in L1 functional wiring, with major implications for our understanding of cortical development.We thank the IBENS Imaging Facility (France BioImaging, supported by ANR-10-INBS-04, ANR-10-LABX-54 MEMO LIFE, and ANR-11-IDEX-000-02 PSLâ Research University, âInvestments for the Futureâ). This work was supported by grants from the Spanish Ministry of Science, Innovation, and Universities (PGC2018-096631-B-I00) and the European Research Council (ERC-2014-CoG-647012) to G.L.-B. N.C. received funding from the Marie SkĆodowska-Curie individual fellowship under the European Unionâs Horizon 2020 research and innovation program (AXO-MATH, grant agreement no. 798326). F.G. received funding from the Agence Nationale de la Recherche (SyTune, ANR-21-CE37-0010), the European Research Council under the European Unionâs Horizon 2020 research and innovation program (NEUROGOAL, grant agreement no.677878), the Region Nouvelle-Aquitaine, and the University of Bordeaux. The Garel laboratory is supported by INSERM, CNRS, ANR-15-CE16-0003, ANR-19-CE16-0017-02, Investissements dâAvenir implemented by ANR-10-LABX-54 MEMO LIFE, ANR-11-IDEX-0001-02 PSLâ Research University, and the European Research Council (ERC-2013-CoG-616080, NImO). I.G. is a recipient of a fellowship from the French Ministry of Research and postdoctoral funding from Labex MemoLife, and S.G. is part of the Ecole des Neurosciences de Paris Ile-de-France network.Peer reviewe
Microglia maintain structural integrity during fetal brain morphogenesis
Microglia (MG), the brain-resident macrophages, play major roles in health and disease via a diversity of cellular states. While embryonic MG display a large heterogeneity of cellular distribution and transcriptomic states, their functions remain poorly characterized. Here, we uncovered a role for MG in the maintenance of structural integrity at two fetal cortical boundaries. At these boundaries between structures that grow in distinct directions, embryonic MG accumulate, display a state resembling post-natal axon-tract-associated microglia (ATM) and prevent the progression of microcavities into large cavitary lesions, in part via a mechanism involving the ATM-factor Spp1. MG and Spp1 furthermore contribute to the rapid repair of lesions, collectively highlighting protective functions that preserve the fetal brain from physiological morphogenetic stress and injury. Our study thus highlights key major roles for embryonic MG and Spp1 in maintaining structural integrity during morphogenesis, with major implications for our understanding of MG functions and brain development.</p