Cortical development

…cell's spatial origin and its changing developmental state. Work in simpler nervous systems provides molecular examples that can inform the study of human cortical development.

…It is accepted, however, that the development of sensory circuits involves intricate interactions between early genetic programs and neuronal activity. Spontaneous activity emerges early in mammalian cortical development, preceding sensory perception and characterized by synchronized patterns of neuronal activity. The precise nature of the inte

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by expansion mutation in the FMR1 gene, which leads to gene silencing via imprinting. Fmr1, located on the X chromosome, encodes the protein FMRP, a pivotal protein for neurogenesis in cortical development (Saffary and Xie, 2011; Casingal et al., 2020). Interestingly, female FXS premutation carriers, especially those with a paternal lineage of the premutation, exhibit an increased incidence of premature ovarian failure (Hundscheid et al., 2000). Despite these findings, the impact of FMRP absence on imprinting mechanisms in the br

…and often find its origins during development. Proper cortical development is directed by a sequence of intrinsic ( transcription factors, local placental-derived 5-HT) and extrinsic (instructing 5-HT and catecholaminergic afferents) events. Recently, our group has shown a functional interplay between the 5-HT and catecholaminergic prefrontal projection systems during development leading to a distortion in PFC cytoarchitecture. Lack o

During cortical development, intrinsic and extrinsic factors regulate how radial glial cells (RGs) proliferate and produce neurons in a highly controlled manner. To date, investigation of the mechanisms regulating radial migration has predominantly relied on studies of cultured cortical slices or employed in utero electroporation strategies. However, these methods are not suitable for investigating the role of gradients of extracellular signals. To address this, we developed an innovative in vitro model where RGs processes support the migration of young pyramidal neurons generated in situ.We p

…microdeletion syndrome, is a rare neurodevelopmental disorder characterized by developmental delay, intellectual disability, and congenital malformations in multiple organ systems, including the brain. KdVS is caused by haploinsufficiency of KANSL1, a gene encoding a protein involved in chromatin remodeling during interphase and microtubule stabilisation during mitosis. KANSL1 is widely expressed in early development, but its role in early brain formation is not characterized. Using patient and genetically-edited induced pluripotent stem

…exome sequencing in a patient with subcortical heterotopia. This is a rare disorder associated with epilepsy and intellectual disability, which may be caused by disturbances in cortical progenitors and /or migrating neurons. Ceramide synthases are important for the biogenesis of ceramides in the endoplasmic reticulum and mitochondria. These are then transferred to the Golgi apparatus for the formation of complex sphingolipids, and in this form further transported to other cell membranes. The major aim of this pr

…transcription factor during development of the nervous system, especially eye and cortical development. It is also a largely studied homeobox gene, but there is limited knowledge about its isoforms and their specific roles. We studie

…along with corticogenesis in early development. However, how imprinted genes regulate these crucial processes in mammals remains elusive. In this study, we investigated the contribution of the maternal or paternal genomes in cortical development and the maintenance of the circadian clock, focusing on the transition from individual cells to a comprehensive neuronal network. To this aim, we used androgenetic (AG) and parthenogenetic (PG) mESCs, generating models with increasing com

GABAergic interneurons (INs) highly impact cortical development. For instance, early postnatal dysregulation of vasoactive intestinal polypeptide (VIP)- expressing GABAergic INs has been shown to impair sensory processing and learning, emerging from adolescence on. Thus, investigating the functional maturation and network integration of VIP-INs is important for understanding brain development. Here, we studied developmental changes in passive and active membrane parameters of VIP-INs and their network integration into the developing neocortex with an emphasised focus on the maturation of their

During mammalian cortical development, how different subtypes of projection neurons are generated by neural stem cells remains a major challenge. Over recent years, the expansion of RNA sequencing technologies has allowed the identification of heterogeneity within the progenitor pool. Understanding how this heterogeneity could participate in the control of cortical fate commitment is an exciting task. Here, we use single-cell RNA sequencing to describe the molecular characteristics of a subpopulation of RGCs that present reduced neurogenic behavior at early embryonic ages to later produce most

…processes, contribute to cortical development and cortical microcircuits formation. Alterations of these delicate processes have often been associated to neurological/neurodevelopmental disorders. However, despite the groundbreaking discovery that spontaneous activity in the embryonic brain can shape regional identities o

…molecular mechanisms involved in the development of axonal connections in the brain. In particular, our aim is to uncover the principles underlying thalamocortical axonal wiring, maintenance and ultimately the rewiring of connections, through an integrated and innovative experimental programme. The development of the thalamocortical wiring requires a precise topographical sorting of its connections. Each thalamic nucleus receives specific sensory information from the environment and projects topographically to its corres