Transcriptional controls over projection neuron fate diversity
The cerebral cortex is the most evolved structure of the brain and the site for higher cognitive functions. It consists of 6 layers, each composed of specific types of neurons. Interconnectivity between cortical areas is critical for sensory integration and sensorimotor transformation. Inter-areal cortical projection neurons are located in all cortical layers and form a heterogeneous population, which send their axon across cortical areas, both within and across hemispheres. How this diversity emerges during development remains largely unknown. Here, we address this question by linking the connectome and transcriptome of developing cortical projection neurons and show distinct maturation paces in neurons with distinct projections, which correlates with the sequential development of sensory and motor functions during postnatal period.
Modulation of oligodendrocyte development and myelination by voltage-gated Ca++ channels
The oligodendrocyte generates CNS myelin, which is essential for normal nervous system function. Thus, investigating the regulatory and signaling mechanisms that control its differentiation and the production of myelin is relevant to our understanding of brain development and of adult pathologies such as multiple sclerosis. We have recently established that the activity of voltage-gated Ca++ channels is crucial for the adequate migration, proliferation and maturation of oligodendrocyte progenitor cells (OPCs). Furthermore, we have found that voltage-gated Ca++ channels that function in synaptic communication between neurons also mediate synaptic signaling between neurons and OPCs. Thus, we hypothesize that voltage-gated Ca++ channels are central components of OPC-neuronal synapses and are the principal ion channels mediating activity-dependent myelination.
Fate and freedom in developing neocortical circuits
During brain development, neurons are born in specialized niches and migrate to target regions where they assemble to form the circuits that underlie mammalian behaviour. During their journey, neurons follow cell-intrinsic, genetic programs transmitted by their mother cells but also environmental cues, which together drive their maturation. Here, focusing on the neocortex, I will discuss recent findings from our laboratory in which we untangle and manipulate the programs at play in progenitors and their daughter neurons to better understand the emergence of cellular diversity in the developing brain.