Identification of a Neuronal Cell Surface Molecule, Plexin, in Mice

doi:10.1006/bbrc.1996.1388

Biochemical and Biophysical Research Communications

Volume 226, Issue 2, 13 September 1996, Pages 524-529

https://doi.org/10.1006/bbrc.1996.1388 Get rights and content

Abstract

We searched for mouse homologues of the cell adhesion protein plexin which was originally found inXenopus,and obtained a cDNA encoding a plexin-like protein. We referred to this protein as mouse plexin 1. The overall amino acid identity between mouse plexin 1 andXenopusplexin was 84%. As in theXenopusplexin, the extracellular segment of mouse plexin 1 protein possessed three cysteine-rich domains which showed significant homology with the cysteine-rich domain of thec-Metproto-oncogene protein product (c-Met protein) and Met-like receptor protein tyrosine kinases. Northern blot analysis indicated that mouse plexin 1 was predominantly expressed in the brain.

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Cited by (33)

PlexinA1 deficiency in BALB/cAJ mice leads to excessive self-grooming and reduced prepulse inhibition
2020, IBRO Reports
Citation Excerpt :
While plexins act as the main receptors for the intracellular signal transmission of Semas, several other membrane-bound proteins also serve as Sema receptors or co-receptors (Toyofuku et al., 2004; Takegahara et al., 2006; Bouvrée et al., 2012; Jongbloets and Pasterkamp, 2014; Worzfeld and Offermanns, 2014), including neuropilins (Nrps), which act in conjunction with PlxnA1 in the ligand-binding subunit for class 3 Semas, PlxnA1 intracellularly transmits signals for class 3 Semas, a group of repulsive axon guidance molecules (Takahashi et al., 1999). PlxnA1 is widely expressed throughout the developing nervous systems, including the auditory system, olfactory system, neocortex, hippocampus, neural retina, and peripheral ganglia (Murakami et al., 2001; Perälä et al., 2005), indicating multiple critical functions in forebrain development (Murakami et al., 2001; Kameyama et al., 1996). Indeed, in a PlxnA1-deficient mouse line on the C57BL/6J background, neuronal progenitor cells of the medial ganglionic eminence were poorly attached to the ventricular surface and displayed reduced proliferative capacity (Andrews et al., 2016), resulting in impaired GABAergic neurogenesis in the embryonic cortex and reduced numbers of striatal projection neurons (Andrews et al., 2016).
PlexinA1 (PlxnA1) is a transmembrane receptor for semaphorins, a large family of proteins that act as axonal guidance cues during nervous system development. However, there are limited studies on PlxnA1 function in neurobehavior. The present study examined if PlxnA1 deficiency leads to behavioral abnormalities in BALB/cAJ mice. PlxnA1 knockout (KO) mice were generated by homologous recombination and compared to wild type (WT) littermates on a comprehensive battery of behavioral tests, including open field assessment of spontaneous ambulation, state anxiety, and grooming, home cage grooming, the wire hang test of muscle strength, motor coordination on the rotarod task, working memory on the Y maze alternation task, cued and contextual fear conditioning, anxiety on the elevated plus maze, sociability to intruders, and sensory processing as measured by prepulse inhibition (PPI). Measures of motor performance, working memory, fear memory, and sociability did not differ significantly between genotypes, while PlxnA1 KO mice displayed excessive self-grooming, impaired PPI, and slightly lower anxiety. These results suggest a crucial role for PlxnA1 in the development and function of brain regions controlling self-grooming and sensory gating. PlxnA1 KO mice may be a valuable model to investigate the repetitive behaviors and information processing deficits characteristic of many neurodevelopmental and psychiatric disorders.
Myt/NZF family transcription factors regulate neuronal differentiation of P19 cells
2011, Neuroscience Letters
During mammalian central nervous system development, neural stem cells differentiate and then mature into various types of neurons. Myelin transcription factor (Myt)/neural zinc finger (NZF) family proteins were first identified as myelin proteolipid protein promoter binding factors and were shown to be involved in oligodendrocyte development. In this study, we found that Myt/NZF family molecules were expressed during neuronal differentiation in vivo and in vitro. Transient over-expression of Myt/NZF family genes could convert undifferentiated P19 cells into neurons without induction by retinoic acid (RA), and the ability of these genes to induce neuronal differentiation was comparable to that of Neurog1 and Neurod1. Additionally, we found that St18 (or NZF-3) was induced by several bHLH transcription factors. When NZF-3 and Neurog1 were co-expressed in P19 cells, the rate of neuronal differentiation was significantly increased. These data suggest not only that NZF-3 works downstream of Neurog1 but also that it plays a crucial role together with Neurog1 in neuronal differentiation.
Diverse functions for the semaphorin receptor PlexinD1 in development and disease
2011, Developmental Biology
Citation Excerpt :
The new molecule was renamed Plexin (Plxn) to highlight its role in organizing the plexiform layers of the neural retina (Ohta et al., 1992; Satoda et al., 1995). Soon the first mammalian Plxns were discovered and found to bind to Semaphorins (Semas), a large family of related extracellular proteins that includes both secreted (class 2 and 3) and membrane-tethered (classes 1, 4–7 and V) forms (Comeau et al., 1998; Kameyama et al., 1996a,b; Maestrini et al., 1996). The first human Plxns were identified in 1996 (Maestrini et al., 1996).
Plexins are a family of single-pass transmembrane proteins that serve as cell surface receptors for Semaphorins during the embryonic development of animals. Semaphorin–Plexin signaling is critical for many cellular aspects of organogenesis, including cell migration, proliferation and survival. Until recently, little was known about the function of PlexinD1, the sole member of the vertebrate-specific PlexinD (PlxnD1) subfamily. Here we review novel findings about PlxnD1's roles in the development of the cardiovascular, nervous and immune systems and salivary gland branching morphogenesis and discuss new insights concerning the molecular mechanisms of PlxnD1 activity.
Failure to confirm an association between the PLXNA2 gene and schizophrenia in a Japanese population
2007, Progress in Neuro-Psychopharmacology and Biological Psychiatry
Plexins are receptors for multiple classes of semaphorins, either alone or in combination with neuropilins. Plexins participate in many cellular events that include axonal repulsion, axonal attraction, cell migration, axon pruning, and synaptic plasticity. PLXNA2 maps to chromosome 1q32. Several linkage studies reported schizophrenia susceptibility loci in the 1q22–42 region. A recent study reported that intronic single nucleotide polymorphisms (SNPs) of PLXNA2 were associated with schizophrenia in a European American population. We attempted to replicate this finding in a Japanese sample of 336 patients with schizophrenia and 304 controls. In addition, we examined 3 non-synonymous SNPs (Arg5Gln, GLn57Arg, and Ala267Thr) in PLXNA2. Genotyping was performed by the TaqMan allelic discrimination assay. There was no significant difference in genotype or allele distribution of either the 4 intronic SNPs or the 3 non-synonymous SNPs between patients and controls. Furthermore, haplotype-based analyses did not provide evidence for an association. These results suggest that PLXNA2 may not play a major role in the development of schizophrenia in our Japanese sample.
Class A plexin expression in axotomized rubrospinal and facial motoneurons
2007, Neuroscience
Citation Excerpt :
Similarly, Western blot analysis of Plxn-A1 protein expression 14 days after facial nerve injury revealed no detectable change in amount of protein present in injured compared with contralateral facial nuclei, supporting our immunohistochemical findings (Fig. 6). Expression of Plxn-A1 in total whole mouse brain protein extract is shown as comparison due to its reported high expression in adult mouse brain tissue (Kameyama et al., 1996). In the present study we compared the mRNA expression patterns of all plexin A family members (Plexin-A1, A2, A3, A4) in axotomized rubrospinal (CNS) and facial (PNS) motoneurons.
The semaphorin family of guidance molecules plays a role in many aspects of neural development, and more recently semaphorins have been implicated to contribute to the failure of injured CNS neurons to regenerate. While semaphorin expression patterns after neural injury are partially understood, little is known about the expression of their signal transducing transmembrane receptors, the plexins. Therefore, in this study, we compared the expression patterns of all class A plexins (Plxn-A1, A2, A3, A4) in mouse CNS (rubrospinal) and peripheral nervous system (PNS)-projecting (facial) motoneurons for up to two weeks following axonal injury. Using in situ hybridization, immunohistochemistry, and Western blot analysis, in rubrospinal neurons, Plxn-A1 mRNA and protein and Plxn-A4 expression did not change as a result of injury while Plxn-A2 mRNA increased and Plxn-A3 mRNA was undetectable. In facial motoneurons, Plxn-A1, -A3 and -A4 mRNA expression increased, Plxn-A2 mRNA decreased while Plxn-A1 protein expression did not change following injury. We demonstrate that with the exception of the absence of Plxn-A3 mRNA in rubrospinal neurons, both injured rubrospinal (CNS) and facial (PNS) neurons maintain expression of all plexin A family members tested. Hence, there are distinct expression patterns of the individual plexin-A family members suggesting that regenerating rubrospinal and facial motoneurons have a differential ability to transduce semaphorin signals.
The expression of plexins during mouse embryogenesis
2005, Gene Expression Patterns
Plexins are large transmembrane proteins that are receptors for semaphorins, either alone or in a complex with neuropilin-1 or -2. Nine different mouse plexins have been found: Plexin-A1–4, -B1–3, -C1 and -D1. The expression and function of plexins in non-neuronal tissues has been poorly characterized, although Plexin-A1 has been shown to have a role during lung and cardiac morphogenesis. We have done an extensive non-radioactive in situ hybridisation survey of Plxna1–a4, Plxnb1 –b3 and Plxnc1 in E14 mouse embryo. At E14, Plxnb3 expression could not be detected by in situ hybridisation. All other plexins studied are widely expressed both in neuronal and non-neuronal tissues. We have also followed the expression patterns of plexins during the development of the kidney, tooth and testis. Plxnb1 and Plxnb2 are expressed in the immature glomeruli and mesenchyme of the developing kidney. In the tooth bud, Plxna1 and Plxnb1 are expressed in the oral epithelium, enamel knot and in both the inner and outer enamel epithelium, whereas the expression of Plxnb2 is more restricted to the inner enamel epithelium. In the testis, Plxna1, Plxnb1 and Plxnc1 are expressed in the developing sex chords. This study shows that during development, plexins are expressed in specific and distinct patterns also in non-neuronal tissues.

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^☆: The Accession Number for mouse plexin 1 is D86948.

²: All correspondence should be addressed to Hajime Fujisawa, Ph.D., Group of Developmental Neurobiology, Laboratory of Developmental Biology, Division of Biological Science, Nagoya University Graduate School of Science, Chikusa-ku, Nagoya 464-01, Japan. Fax: 052-789-2979. E-mail: [email protected].

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Regular ArticleIdentification of a Neuronal Cell Surface Molecule, Plexin, in Mice☆

Abstract

Regular Article
Identification of a Neuronal Cell Surface Molecule, Plexin, in Mice☆