Abstract
Fibronectin and leucine-rich transmembrane (FLRT) proteins are necessary for various developmental processes and in pathological conditions. FLRT2 acts as a homophilic cell adhesion molecule, a heterophilic repulsive ligand of Unc5/Netrin receptors, and a synaptogenic molecule; the last feature is mediated by binding to latrophilins. Although the function of FLRT2 in regulating cortical migration at the late gestation stage has been analyzed, little is known about the expression pattern of FLRT2 during postnatal central nervous system (CNS) development. In this study, we used Flrt2-LacZ knock-in (KI) mice to analyze FLRT2 expression during CNS development. At the early postnatal stage, FLRT2 expression was largely restricted to several regions of the striatum and deep layers of the cerebral cortex. In adulthood, FLRT2 expression was more prominent in the cerebral cortex, hippocampus, piriform cortex (PIR), nucleus of the lateral olfactory tract (NLOT), and ventral medial nucleus (VM) of the thalamus, but lower in the striatum. Notably, in the hippocampus, FLRT2 expression was confined to the CA1 region and partly localized on pre- and postsynapses whereas only few expression was observed in CA3 and dentate gyrus (DG). Finally, we observed temporally limited FLRT2 upregulation in reactive astrocytes around lesion sites 7 days after thoracic spinal cord injury. These dynamic changes in FLRT2 expression may enable multiple FLRT2 functions, including cell adhesion, repulsion, and synapse formation in different regions during CNS development and after spinal cord injury.
Highlights
The mammalian cerebral cortex is a highly organized laminar structure with six layers
The deep layer neurons expressed FLRT2 at the early stages, but FLRT2 expression was expanded in the adult mice (Figures 1G–I and Supplementary Figure 2)
Weak and moderate FLRT2 expression was observed in the lateral amygdala nucleus (LA) at P7 and adulthood, respectively
Summary
The mammalian cerebral cortex is a highly organized laminar structure with six layers. The cortical plate develops in an inside-out pattern, i.e., later-born neurons migrate outward through neurons born earlier After arriving at their final destinations, neurons extend their axons and establish synaptic connections with neurons in other layers and regions, allowing. FLRT2 Expression in Postnatal CNS each layer and region to exhibit characteristic features Axon guidance molecules such as Netrin, Ephrins, Semaphorins, and Slits are involved in organizing the precise positioning and connection of neurons (Chen et al, 2008; Torii et al, 2009; Gonda et al, 2020; Yamagishi et al, 2021). Recent work showed that the TEN2–LPHN3–FLRT3 ternary complex is important for the formation of synaptic properties (Sando et al, 2019; Li et al, 2020)
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