A Nuclear Belt Fastens on Neural Cell Fate

Abstract

Successful embryonic and adult neurogenesis require proliferating neural stem and progenitor cells that are intrinsically and extrinsically guided into a neuronal fate. In turn, migration of new-born neurons underlies the complex cytoarchitecture of the brain. Proliferation and migration are therefore essential for brain development, homeostasis and function in adulthood. Among several tightly regulated processes involved in brain formation and function, recent evidence points to the nuclear envelope (NE) and NE-associated components as critical new contributors. Classically, the NE was thought to merely represent a barrier mediating selective exchange between the cytoplasm and nucleoplasm. However, research over the past two decades has highlighted more sophisticated and diverse roles for NE components in progenitor fate choice and migration of their progeny by tuning gene expression via interactions with chromatin, transcription factors and epigenetic factors. Defects in NE components lead to neurodevelopmental impairments, whereas age-related changes in NE components are proposed to influence neurodegenerative diseases. Thus, understanding the roles of NE components in brain development, maintenance and aging is likely to reveal new pathophysiological mechanisms for intervention. Here, we review recent findings for the previously underrepresented contribution of the NE in neuronal commitment and migration, and envision future avenues for investigation.

Epigenetic aging in adult neurogenesis

“…Accumulating evidence also suggests a critical importance of nuclear structural proteins in the control of NSC behavior (Kinkel & Prince, 2010;Mestres et al, 2022). Intriguingly, two recent studies have identified reduced levels of the nuclear lamina protein lamin B1 as one factor underlying the age-related reduction in adult hippocampal neurogenesis (Bedrosian et al, 2020;Bin Imtiaz et al, 2021).…”

“…The nuclear envelope and its associated proteins are instructive for the nuclear architecture, not only by determining shape and organization of the nucleus but also through their direct roles in gene regulation. Accumulating evidence also suggests a critical importance of nuclear structural proteins in the control of NSC behavior (Kinkel & Prince, 2010; Mestres et al, 2022). Intriguingly, two recent studies have identified reduced levels of the nuclear lamina protein lamin B1 as one factor underlying the age‐related reduction in adult hippocampal neurogenesis (Bedrosian et al, 2020; Bin Imtiaz et al, 2021).…”

“…Lamins are important structural components of the nuclear envelope which bind heterochromatin at the inner nuclear membrane and interact with epigenetic modifiers to control gene expression (Mestres et al, 2022). Neural cells show cell type‐specific lamin B1 expression patterns, with NSCs and neuroblasts expressing high levels of lamin B1 which decrease during neuronal maturation (Bedrosian et al, 2020; Bin Imtiaz et al, 2021).…”

From Youthful Vigor to Aging Decline: Unravelling the Intrinsic and Extrinsic Determinants of Hippocampal Neural Stem Cell Aging

“…In addition to their role as a barrier to the segregation of toxic molecules during NSC division, components of the nuclear envelope such as lamins help to anchor chromatin and control gene expression through interaction with epigenetic modifiers [ 104 , 105 , 106 ]. During aging, lamin B1 expression decreases in hippocampal NSCs, resulting in a reshaping of the nuclear architecture [ 39 , 40 , 107 ].…”

High Fat Diet Multigenerationally Affects Hippocampal Neural Stem Cell Proliferation via Epigenetic Mechanisms

“…NSPCs represent the cellular source of newborn neurons in the dentate gyrus of the hippocampus, and their fate is highly modulated by metabolic signals [ 7 , 8 ]. Epigenetic mechanisms are key factors controlling the neural fate of NSPCs and they dynamically regulate central nervous system development and adult neurogenesis [ 9 , 10 ]. Here, we demonstrate that maternal HFD multigenerationally impairs the hippocampal neurogenic niche in the descendants until the third generation.…”