Slitrk gene duplication and expression in the developing zebrafish nervous system

Abstract

Background: The Slitrk family of leucine-rich repeat (LRR) transmembrane proteins bears structural similarity to the Slits and the Trk receptor families, which exert well-established roles in directing nervous system development. Slitrks are less well understood, although they are highly expressed in the developing vertebrate nervous system. Moreover, slitrk variants are associated with several sensory and neuropsychiatric disorders, including myopia, deafness, obsessive-compulsive disorder (OCD), schizophrenia, and Tourette syndrome. Loss-of-function studies in mice show that Slitrks modulate neurite outgrowth and inhibitory synapse formation, although the molecular mechanisms of Slitrk function remain poorly characterized. Results: As a prelude to examining the functional roles of Slitrks, we identified eight slitrk orthologs in zebrafish and observed that seven of the eight orthologs were actively transcribed in the nervous system at embryonic, larval, and adult stages. Similar to previous findings in mice and humans, zebrafish slitrks exhibited unique but overlapping spatial and temporal expression patterns in the developing brain, retina, and spinal cord. Conclusions: Zebrafish express Slitrks in the developing central nervous system at times and locations important to neuronal morphogenesis and synaptogenesis. Future studies will use zebrafish as a convenient, cost-effective model organism to characterize the functional roles of Slitrks in nervous system development. Developmental Dynamics 243:339-349, 2014. V C 2013 Wiley Periodicals, Inc.

Developmental control of noradrenergic system by SLITRK1 and its implications in the pathophysiology of neuropsychiatric disorders

“…Phylogenetically, SLITRK1 and other SLITRK family proteins exist in vertebrates; however, no orthologs have been identified in invertebrates, including cephalochordates and urochordates. In zebrafish embryos, Slitrk1 expression was detected in the thalamus, hypothalamus, tegmentum, medulla oblongata, and retina ( Round et al, 2014 ). Evolutionary conserved expression profiles have been reported between mouse and chicken (mantle layer and motor neurons of the developing spinal cord; Aruga and Mikoshiba, 2003 ) and between mouse and zebrafish (ganglionic cell layer and inner nuclear layer of the developing retina; Beaubien and Cloutier, 2009 ; Round et al, 2014 ).…”

“…In zebrafish embryos, Slitrk1 expression was detected in the thalamus, hypothalamus, tegmentum, medulla oblongata, and retina ( Round et al, 2014 ). Evolutionary conserved expression profiles have been reported between mouse and chicken (mantle layer and motor neurons of the developing spinal cord; Aruga and Mikoshiba, 2003 ) and between mouse and zebrafish (ganglionic cell layer and inner nuclear layer of the developing retina; Beaubien and Cloutier, 2009 ; Round et al, 2014 ).…”

Upregulation of SLITRK5 in patients with epilepsy and in a rat model

“…SLIT and NTRK‐like protein‐5 (SLITRK5) and its family members, as neuronal transmembrane proteins, are broadly expressed in central nervous system (Aruga et al., 2003; Beaubien & Cloutier, 2009), modulating a wide variety of important developmental events, including neurite outgrowth, axon guidance, target selection, dendrite arborization, and synaptogenesis (Round et al., 2014; Song et al., 2017). SLITRK5 was generally expressed in the developing central nervous system at times and locations that are important to neuronal morphogenesis and synaptogenesis (Beaubien & Cloutier, 2009; Round et al., 2014), as well as in embryonic stem cells, subsets of endothelial cells, hematopoietic stem cells, and in leukemia and lymphoma cells (Aruga & Mikoshiba, 2003).…”

“…SLIT and NTRK-like protein-5 (SLITRK5) and its family members, as neuronal transmembrane proteins, are broadly expressed in central nervous system Beaubien & Cloutier, 2009), modulating a wide variety of important developmental events, including neurite outgrowth, axon guidance, target selection, dendrite arborization, and synaptogenesis (Round et al, 2014;. SLITRK5 was generally expressed in the developing central nervous system at times and locations that are important to neuronal morphogenesis and synaptogenesis (Beaubien & Cloutier, 2009;Round et al, 2014), as well as in embryonic stem cells, subsets of endothelial cells, hematopoietic stem cells, and in leukemia and lymphoma cells . SLITRK5 is associated with many neurological disorders (Liu et al, 2022), which can be combined with the synaptic adhesion molecules (SAMs), type IIa receptor protein tyrosine phosphatase (RPTP), controlling synapse formation, thus regulating the connections between neurons (Beaubien et al, 2016;O'Sullivan et al, 2012;Shmelkov et al, 2001;Song et al, 2015).Additionally, SLITRK5 is associated with a variety of tumors, such as brain glioma, thyroid tumors, gastric cancer, nasopharyngeal carcinoma, lung squamous cell carcinoma, and colorectal tumor (Haoran & Yanhua, 2018;Heiliger et al, 2012;Hesson et al, 2016;Ju et al, 2020;Li et al, 2016;Park et al, 2016).…”

The Role of SliTrk5 in Central Nervous System

“…Scholars identified the SliTrk family proteins originally in a screen for genes that were differentially expressed in the neural tube defects mice [ 2 ]. Correspondingly, it has also been verified that six members of the SliTrk family located in three different loci: chromosome 3 (SliTrk3), chromosome 13 (SliTrk1, SliTrk5, and SliTrk6), and the X chromosome (SliTrk2 and SliTrk4) [ 3 ], all of which are generally expressed in the developing central nervous system at times and locations that are important to neuronal morphogenesis and synaptogenesis [ 4 , 5 ], as well as in brain tumors, embryonic stem cells, subsets of endothelial cells, hematopoietic stem cells, and in leukemia and lymphoma cells [ 6 ], but vary within the family. For example, SliTrk5 is significantly expressed in the CA1 region of hippocampal [ 7 ] and also in occipital and frontal lobes of brain, spinal cord, medulla, and in early hematopoietic progenitors [ 8 , 9 ], whereas SliTrk1 is expressed in the mature neurons, SliTrk2 is highly expressed in the ventricular layer, and SliTrk6 shows compartmentalized expression in diencephalon.…”