Abstract
During development of the zebrafish embryo, glycine signaling promotes the differentiation of neural stem cells (NSCs). We found that glycine signaling suppresses the expression of Ligand of Numb X1 (lnx1, Ligand of numb protein-x1), a gene of unknown function during NSC differentiation that is selectively expressed in the embryonic central nervous system (CNS). As a consequence, Numb levels were stabilized and Notch activity (measured as her4.1 expression) was reduced, promoting NSC differentiation. These consequent actions were blocked by knockdown of lnx1. In contrast, lnx1 overexpression increased NSC proliferation and led to defects of neural tube closure at the early stages of development. Thus, our data provide evidence that glycine/lnx1 signaling modulates NSC proliferation by regulation of Notch signaling.
Highlights
During neuronal development an early spontaneous electrical activity is generated in neural stem cells (NSCs) as an essential step for their proliferation, migration and differentiation (Spitzer, 2006) and involves several neurotransmitters including glutamate, GABA and glycine (Demarque et al, 2002; Scain et al, 2010)
We demonstrated with different approaches that disruption of glycine signaling induced an overexpression of lnx1 in NSCs (Figure 1)
We showed that disruption of glycine signaling by knockdown of glycine receptors (Glrs) induced an overexpression of lnx1 in NSCs
Summary
During neuronal development an early spontaneous electrical activity is generated in neural stem cells (NSCs) as an essential step for their proliferation, migration and differentiation (Spitzer, 2006) and involves several neurotransmitters including glutamate, GABA and glycine (Demarque et al, 2002; Scain et al, 2010). An RNA sequencing analysis revealed that glycine signaling regulates several pathways in NSC development (Samarut et al, 2016) as well as some outlying genes, with Ligand of numb protein-x1 (lnx1) among the most affected. Numb is well-known to be an inhibitor of Notch signaling (Roegiers and Jan, 2004; Mcgill et al, 2009), but further elucidations are required to understand how Notch and lnx activity correlates with other pathways to fine-tune neuronal development
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