Nuclear receptors in neural stem/progenitor cell homeostasis

Abstract

In the central nervous system, embryonic and adult neural stem/progenitor cells (NSCs) generate the enormous variety and huge numbers of neuronal and glial cells that provide structural and functional support in the brain and spinal cord. Over the last decades, nuclear receptors and their natural ligands have emerged as critical regulators of NSC homeostasis during embryonic development and adult life. Furthermore, substantial progress has been achieved towards elucidating the molecular mechanisms of nuclear receptors action in proliferative and differentiation capacities of NSCs. Aberrant expression or function of nuclear receptors in NSCs also contributes to the pathogenesis of various nervous system diseases. Here, we review recent advances in our understanding of the regulatory roles of steroid, non-steroid, and orphan nuclear receptors in NSC fate decisions. These studies establish nuclear receptors as key therapeutic targets in brain diseases.

A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes

“…We observed upregulation of Ascl1, Nr2f1, Crabp2, and Nr6a1 genes (Appendix Fig S1B) in slow/slow NPCs and AGGs. Their overexpression has been previously shown to suppress proliferation of progenitor cells, induce neurogenesis and neuronal maturation (Chanda et al, 2014;Gkikas et al, 2017), and could explain the premature differentiation observed in slow/slow NSCs. In parallel, we observed that the EGF receptor (EGFR) was twofold downregulated in slow/slow NPCs (Table EV2).…”

The ENDpoiNTs Project: Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity

“…Yet, GR activation during brain development inhibits the migration of post-mitotic neurons in rodents and decreases proliferation and cell survival in both rodent and human neuronal stem cells. In humans, high doses of a GR agonist during pregnancy leads to severe pathologies in children such as cognitive and motor disorders [34].…”

Cell Signaling in Neuronal Stem Cells

“…Estrogen receptors (ERs) are part of the family of NR3A nuclear receptors and also known as steroid hormone receptors. The estrogen receptor subtypes ER alpha (NR3A1) and ER beta (NR3A2) are expressed in the nucleus, cytoplasm and membrane [ 14 ]. It has been shown that the activation of estrogen receptors by 17 beta estradiol (E2) regulates the proliferation of embryonic NSCs mediated by overexpression of the cyclin-dependent kinase inhibitor, p21 Cip1 [ 15 ], while promoting the proliferation and differentiation to glial cells of NSC embryonic rat in the absence of mitogens Epidermal growth factor (EGF), Fibroblast growth factor-2 (FGF-2) or differentiation factors [ 16 ].…”