Search results for "Semaphorin"
showing 10 items of 16 documents
Sema3a plays a role in the pathogenesis of CHARGE syndrome
2018
CHARGE syndrome is an autosomal dominant malformation disorder caused by heterozygous loss of function mutations in the chromatin remodeler CHD7. Chd7 regulates the expression of Sema3a, which also contributes to the pathogenesis of Kallmann syndrome, a heterogeneous condition with the typical features hypogonadotropic hypogonadism and an impaired sense of smell. Both features are common in CHARGE syndrome suggesting that SEMA3A may provide a genetic link between these syndromes. Indeed, we find evidence that SEMA3A plays a role in the pathogenesis of CHARGE syndrome. First, Chd7 is enriched at the Sema3a promotor in neural crest cells and loss of function of Chd7 inhibits Sema3a expression…
Semaphorins in Adult Nervous System Plasticity and Disease
2021
Semaphorins, originally discovered as guidance cues for developing axons, are involved in many processes that shape the nervous system during development, from neuronal proliferation and migration to neuritogenesis and synapse formation. Interestingly, the expression of many Semaphorins persists after development. For instance, Semaphorin 3A is a component of perineuronal nets, the extracellular matrix structures enwrapping certain types of neurons in the adult CNS, which contribute to the closure of the critical period for plasticity. Semaphorin 3G and 4C play a crucial role in the control of adult hippocampal connectivity and memory processes, and Semaphorin 5A and 7A regulate adult neuro…
New functions of Semaphorin 3E and its receptor PlexinD1 during developing and adult hippocampal formation
2018
AbstractThe development and maturation of cortical circuits relies on the coordinated actions of long and short range axonal guidance cues. In this regard, the class 3 semaphorins and their receptors have been seen to be involved in the development and maturation of the hippocampal connections. However, although the role of most of their family members have been described, very few data about the participation of Semaphorin 3E (Sema3E) and its receptor PlexinD1 during the development and maturation of the entorhino-hippocampal (EH) connection are available. In the present study, we focused on determining their roles both during development and in adulthood. We determined a relevant role for…
Reduced Sympathetic Innervation in Endometriosis is Associated to Semaphorin 3C and 3F Expression
2016
Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic inner…
Semaphorin and plexin gene expression is altered in the prefrontal cortex of schizophrenia patients with and without auditory hallucinations
2015
Auditory hallucinations (AH) are clinical hallmarks of schizophrenia, however little is known about molecular genetics of these symptoms. In this study, gene expression profiling of postmortem brain samples from prefrontal cortex of schizophrenic patients without AH (SNA), patients with AH (SA) and control subjects were compared. Genome-wide expression analysis was conducted using samples of three individuals of each group and the Affymetrix GeneChip Human-Gene 1.0 ST-Array. This analysis identified the Axon Guidance pathway as one of the most differentially expressed network among SNA, SA and CNT. To confirm the transcriptome results, mRNA level quantification of seventeen genes involved i…
Mice lacking Plexin-B3 display normal CNS morphology and behaviour
2009
Semaphorins and their receptors, plexins, have emerged as important regulators of a multitude of biological processes. Plexin-B3 has been shown to be selectively expressed in postnatal oligodendrocytes. In contrast to the well-characterized Plexin-A family and the Plexin-B family members Plexin-B1 and -B2, no data are available on the functional role of Plexin-B3 in the central nervous system in vivo. Here we have elucidated the functional significance of Plexin-B3 by generating and analyzing constitutive knock-out mice. Plexin-B3-deficient mice were found to be viable and fertile. A systematic histological analysis revealed no morphological defects in the brain or spinal cord of mutant ani…
Semaphorin 6A Improves Functional Recovery in Conjunction with Motor Training after Cerebral Ischemia
2010
Stroke is a major health problem in industrialized societies. Despite numerous attempts at developing acute stroke therapies aimed at minimizing acute infarct development, the only approved therapy so far is recombinant tissue plasminogen activator (rtPA). In recent years, the attention of the stroke community has therefore also put increased emphasis on understanding processes of post-stroke recovery, and their potential exploitability for therapeutic purposes. The brain has a remarkable ability to adapt to changes after stroke. Mechanisms that contribute to this plasticity are re-mapping and expansion of cortical areas to neighboring regions of functional motor cortex areas after injury […
A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability.
2016
AbstractSemaphorins are a large family of secreted and membrane-associated proteins necessary for wiring of the brain. Semaphorin 5A (SEMA5A) acts as a bifunctional guidance cue, exerting both attractive and inhibitory effects on developing axons. Previous studies have suggested that SEMA5A could be a susceptibility gene for autism spectrum disorders (ASDs). We first identified a de novo translocation t(5;22)(p15.3;q11.21) in a patient with ASD and intellectual disability (ID). At the translocation breakpoint on chromosome 5, we observed a 861-kb deletion encompassing the end of the SEMA5A gene. We delineated the breakpoint by NGS and observed that no gene was disrupted on chromosome 22. We…
Expression of semaphorin 3A and neuropilin 1 with clinicopathological features and survival in human tongue cancer
2012
Objective: To investigate the association between semaphorin 3A (SEMA 3A) and its receptor neuropilin 1 (NRP1) and the clinicopathologic characteristics of patients with tongue cancer. Study Design: Forty-three tongue squamous cell carcinoma specimens were included. Immunohistochemical staining of SEMA3A and NRP1 was performed on 15 normal tongue epithelium specimens and the 43 tumour specimens. Immunoreactivity was evaluated based on the staining intensity and distribution score. Statistical analyses were performed using Chi-squared and Spearman tests and Kaplan-Meier analysis. Results: SEMA3A was significantly down-regulated in tongue cancer compared with normal tongue (P=0.025), while NR…
Genetic dissection of plexin signaling in vivo
2014
Mammalian plexins constitute a family of transmembrane receptors for semaphorins and represent critical regulators of various processes during development of the nervous, cardiovascular, skeletal, and renal system. In vitro studies have shown that plexins exert their effects via an intracellular R-Ras/M-Ras GTPase-activating protein (GAP) domain or by activation of RhoA through interaction with Rho guanine nucleotide exchange factor proteins. However, which of these signaling pathways are relevant for plexin functions in vivo is largely unknown. Using an allelic series of transgenic mice, we show that the GAP domain of plexins constitutes their key signaling module during development. Mice …