The 2016 Bernard Sachs Lecture: Timing in Morphogenesis and Genetic Gradients During Normal Development and in Malformations of the Nervous System

Pediatric Neurology
Harvey B Sarnat

Abstract

Nervous system development is quadradimensional. Both normal ontogenesis and developmental malformations are explained in the context of the fourth dimension, timing. Timing of the onset of either the genetic expression of a mutation or an epigenetic event that may be teratogenic is primordial in determining morphogenesis and the forms of malformations with their functional consequences. Multiple genotypes may cause similar phenotypes or a single genotype with different degrees of retained normal genetic expression may result in variable phenotypes. In this treatise, examples are presented of these principles, including both delayed and precocious maturation of processes such as synaptogenesis that may be out of synchrony with other simultaneous processes of neuronal maturation. In postzygotic somatic mosaicism, timing of onset determines not only the character but also the extent of a lesion; focal cortical dysplasia IIb and hemimegalencephaly are the same disease, both sharing activation of the mTOR pathway as the primary mechanism; the difference is timing of onset within the 33 mitotic cycles of the periventricular neuroepithelium. Genetic expression often follows gradients along the 3 axes of the neural tube. Defective gra...Continue Reading

Citations

Nov 17, 2019·Environmental Science and Pollution Research International·Afusat J JubrilVictor O Taiwo
Apr 25, 2019·Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz·UNKNOWN Fachübergreifender Arbeitskreis „Bundesweites Pollenmonitoring“
Feb 11, 2020·Frontiers in Cellular Neuroscience·Lakshmi SubramanianMercedes F Paredes

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