Evaluation of advances in cortical development using model systems

Abstract

Compared with that of even the closest primates, the human cortex displays a high degree of specialization and expansion that largely emerges developmentally. Although decades of research in the mouse and other model systems has revealed core tenets of cortical development that are well preserved across mammalian species, small deviations in transcription factor expression, novel cell types in primates and/or humans, and unique cortical architecture distinguish the human cortex. Importantly, many of the genes and signaling pathways thought to drive human‐specific cortical expansion also leave the brain vulnerable to disease, as the misregulation of these factors is highly correlated with neurodevelopmental and neuropsychiatric disorders. However, creating a comprehensive understanding of human‐specific cognition and disease remains challenging. Here, we review key stages of cortical development and highlight known or possible differences between model systems and the developing human brain. By identifying the developmental trajectories that may facilitate uniquely human traits, we highlight open questions in need of approaches to examine these processes in a human context and reveal translatable insights into human developmental disorders.

Adverse effects of gestational ω‐3 and ω‐6 polyunsaturated fatty acid imbalance on the programming of fetal brain development

“…Thus, disruption of these processes by environmental factors will likely provoke long-lived modifications to brain structure and, ultimately, function. 2,3 In principle, two models of developmental "programming" (that is, a lasting change to cell type identity and function) are distinguished: (i) direct "fetal programming", when an intrauterine insult directly alters cellular identity to an extent that it manifests in somatic and/or mental illnesses later in life. Such diseases include schizophrenia, depression, and even the emergence of neurodegenerative diseases.…”

“…This is because the developing CNS is particularly vulnerable during intrauterine development to metabolic compromise given the exceptional energy demands of its many cell types that are being generated (including neurons, astroglia, microglia, oligodendroglia, vasculature), their protracted movements (migration), morphogenesis, and assembly into functional circuits. Thus, disruption of these processes by environmental factors will likely provoke long‐lived modifications to brain structure and, ultimately, function 2,3 . In principle, two models of developmental “programming” (that is, a lasting change to cell type identity and function) are distinguished: (i) direct “fetal programming”, when an intrauterine insult directly alters cellular identity to an extent that it manifests in somatic and/or mental illnesses later in life.…”