Biomaterial Database

ECE2 regulates neurogenesis and neuronal migration during human cortical development. 2020

Isabel Y Buchsbaum, and Pavel Kielkowski, and Grazia Giorgio, and Adam C O'Neill, and Rossella Di Giaimo, and Christina Kyrousi, and Shahryar Khattak, and Stephan A Sieber, and Stephen P Robertson, and Silvia Cappello

Max Planck Institute of Psychiatry, Munich, Germany.

During embryonic development, excitatory projection neurons migrate in the cerebral cortex giving rise to organised layers. Periventricular heterotopia (PH) is a group of aetiologically heterogeneous disorders in which a subpopulation of newborn projection neurons fails to initiate their radial migration to the cortex, ultimately resulting in bands or nodules of grey matter lining the lateral ventricles. Although a number of genes have been implicated in its cause, currently they only satisfactorily explain the pathogenesis of the condition for 50% of patients. Novel gene discovery is complicated by the extreme genetic heterogeneity recently described to underlie its cause. Here, we study the neurodevelopmental role of endothelin-converting enzyme-2 (ECE2) for which two biallelic variants have been identified in two separate patients with PH. Our results show that manipulation of ECE2 levels in human cerebral organoids and in the developing mouse cortex leads to ectopic localisation of neural progenitors and neurons. We uncover the role of ECE2 in neurogenesis, and mechanistically, we identify its involvement in the generation and secretion of extracellular matrix proteins in addition to cytoskeleton and adhesion.

UI	MeSH Term	Description	Entries
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D002465	Cell Movement	The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.	Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D054091	Periventricular Nodular Heterotopia	A disorder resulting from a defect in the pattern of neuronal migration in which ectopic collections of neurons lie along the lateral ventricles of the brain or just beneath, contiguously or in isolated patches.	Bilateral Periventricular Nodular Heterotopia,Familial Nodular Heterotopia,Heterotopia, Familial Nodular,Heterotopia, Periventricular, X-Linked Dominant,Nodular Heterotopia, Bilateral Periventricular,Periventricular Heterotopia,Periventricular Heterotopia, X-Linked,Periventricular Nodular Heterotopia 1,Familial Nodular Heterotopias,Heterotopia, Periventricular,Heterotopia, Periventricular Nodular,Heterotopia, X-Linked Periventricular,Nodular Heterotopia, Familial,Nodular Heterotopia, Periventricular,Periventricular Heterotopia, X Linked,Periventricular Heterotopias,Periventricular Nodular Heterotopias,X-Linked Periventricular Heterotopia,X-Linked Periventricular Heterotopias
D055495	Neurogenesis	Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons.	Neurogeneses