Developmental cell death regulates lineage-related interneuron-oligodendroglia functional clusters and oligodendrocyte homeostasis

• Published in: Nature communications 2019-09, Vol.10 (1), p.4249-13, Article 4249
• Main Authors: Orduz, David, Benamer, Najate, Ortolani, Domiziana, Coppola, Eva, Vigier, Lisa, Pierani, Alessandra, Angulo, María Cecilia
• Format: Article
• Language: English
• Subjects: 13; 13/51; 14; 14/1; 14/19; 631/378/1934; 631/378/2596/1705; 64/60; 9/74; Animals; Apoptosis; Apoptosis - physiology; Cell death; Cell interactions; Central Nervous System - cytology; Central Nervous System - embryology; Clusters; Cortex; Density; Embryos; Female; GABAergic Neurons - cytology; Glial stem cells; Homeodomain Proteins - metabolism; Homeostasis; Humanities and Social Sciences; Interneurons; Interneurons - cytology; Interneurons - metabolism; Life Sciences; Male; Mice; Mice, Transgenic; multidisciplinary; Myelination; Nerve Tissue Proteins - metabolism; Neural networks; Neurogenesis - physiology; Oligodendrocyte Precursor Cells - metabolism; Oligodendrocytes; Oligodendroglia - cytology; Oligodendroglia - metabolism; Population; Populations; Science; Science (multidisciplinary); Transcription factors; Transgenic animals; γ-Aminobutyric acid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-11904-4

The first wave of oligodendrocyte precursor cells (firstOPCs) and most GABAergic interneurons share common embryonic origins. Cortical firstOPCs are thought to be replaced by other OPC populations shortly after birth, maintaining a consistent OPC density and making postnatal interactions between firstOPCs and ontogenetically-related interneurons unlikely. Challenging these ideas, we show that a cortical firstOPC subpopulation survives and forms functional cell clusters with lineage-related interneurons. Favored by a common embryonic origin, these clusters display unexpected preferential synaptic connectivity and are anatomically maintained after firstOPCs differentiate into myelinating oligodendrocytes. While the concomitant rescue of interneurons and firstOPCs committed to die causes an exacerbated neuronal inhibition, it abolishes interneuron-firstOPC high synaptic connectivity. Further, the number of other oligodendroglia populations increases through a non-cell-autonomous mechanism, impacting myelination. These findings demonstrate unprecedented roles of interneuron and firstOPC apoptosis in regulating lineage-related cell interactions and the homeostatic oligodendroglia density. During cortical development the first wave of oligodendrocyte precursor cells (OPCs) completely disappear by programmed cell death, so that it is presumed that this OPC population does not play a role at postnatal stages. In this study, authors use lineage tracing in different transgenic mice to show that a subpopulation of OPCs from the first wave survives at postnatal stages and display a preferential synaptic connectivity with their ontogenetically-related interneurons compared to other OPCs or interneurons