Biology subjects

Bessieres, B.

Publications and source records attributed to Bessieres, B..

3 recordsLinked to original sources

bioRxiv2022

A cell fate decision map reveals abundant direct neurogenesis in the human developing neocortex

The human neocortex has undergone strong evolutionary expansion, largely due to an increased progenitor population, the basal radial glial (bRG) cells. These cells are responsible for the production of a diversity of cell types, but the successive cell fate decisions taken by individual progenitors remains unknown. Here, we developed a semi-automated live/fixed correlative imaging method to generate a map of bRG cell division modes in early fetal tissue and cerebral organoids. Through the analysis of over 1,000 dividing progenitors, we show that bRG cells undergo abundant symmetric amplifying divisions, followed by frequent direct neurogenic divisions, bypassing intermediate progenitors. These direct neurogenic divisions are more abundant in the upper part of the subventricular zone. We furthermore demonstrate asymmetric Notch activation in the self-renewing daughter cells, independently of basal fiber inheritance. Our results reveal a remarkable conservation of fate decisions in cerebral organoids, supporting their value as models of early human neurogenesis.

developmental biology↗

bioRxiv2022

Origin of congenital coronary arterio-ventricular fistulae from anomalous epicardial and myocardial development

AimsIn this work we investigated the embryonic origin of coronary arterio-ventricular connections, known as coronary artery fistulas (CAF), a congenital heart disease associated to postnatal and adult changes in systemic hemodynamics that may cause cardiac ischemia. Methods and resultswe have used different animal models (mouse and avian embryos) to experimentally model CAF morphogenesis. Conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick and quail embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Additional transcriptomics and in vitro analyses were performed to better understand how arterio-ventricular connections are originated in the embryonic heart. Our results show myocardial discontinuities in the developing heart of mutant mice presenting epicardial defects and avian embryos submitted to a physical cryodamage of the ventricle. These ventricular discontinuities promote the formation of endocardial pouch-like structures resembling human CAF. The structure of these CAF-like anomalies was compared with histopathological data from a human CAF, showing histomorphological and immunochemical similarities. Both human and mutant mouse hearts showed similar anomalies in the compaction of the ventricular myocardium. In vitro experiments showed the abnormal contact between the epicardium and the endocardium promote the precocious differentiation of epicardial cells to smooth muscle. ConclusionOur work suggests that myocardial discontinuities in the embryonic ventricular wall are a causative of CAF. These discontinuities would promote the early contact of the endocardium with epicardial-derived coronary progenitors at the cardiac surface, leading to ventricular endocardial extrusion, precocious differentiation of coronary smooth muscle cells, and the formation of pouch-like aberrant coronary-like structures in direct connection with the ventricular lumen. Translational perspectiveCongenital coronary artery fistulas (CAFs) lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation and failure. Unfortunately, and despite their clinical relevance, the origins these congenital anomalies remain unknown. In this work, we provide information on the developmental mechanisms involved in the formation of CAFs that is relevant for their early diagnosis and prevention.

developmental biology↗

bioRxiv2021

Neuronal activity-driven oligodendrogenesis in selected brain regions is required for episodic memories

The formation of long-term episodic memories requires the activation of molecular mechanisms in several regions of the medial temporal lobe, including the hippocampus and anterior cingulate cortex (ACC). The extent to which these regions engage distinct mechanisms and cell types to support memory formation is not well understood. Recent studies reported that oligodendrogenesis is essential for learning and long-term memory; however, whether oligodendrocyte lineage cells are required only in selected brain regions is still unclear. Also still unknown are the temporal kinetics of oligodendrocyte lineage cells involvement in memory processes and whether these cells are engaged in response to neuronal activity. Here we show that in rats and mice, episodic learning rapidly increases the oligodendrogenesis and myelin biogenesis transcripts Olig2, Myrf, Mbp, and Plp1 as well as oligodendrocyte precursor cells (OPC) proliferation and differentiation in the ACC, but not in the dorsal hippocampus (dHC). Region-specific knockdown or knockout of Myrf, a regulator of oligodendrocyte differentiation, revealed that cells of the oligodendrocyte lineage are required for memory formation in the ACC but not the dHC. Chemogenetic neuronal silencing in the ACC showed that neuronal activity is critical for learning-induced OPC proliferation. Hence, activity-driven oligodendrocyte lineage cells in the ACC, but not dHC, are critical for the formation of episodic memories. Impact statementOligodendrocyte lineage cells are required in the anterior cingulate cortex but not in the hippocampus for long-term memory formation.

neuroscience↗