Biomedical subjects

H Chen

Publications and source records attributed to H Chen.

At least 433 records · Page 24Linked to original sources

PubMed2000

Intracellular pH modulation of ADF/cofilin proteins.

The ADF/cofilin (AC) proteins are necessary for the high rates of actin filament turnover seen in vivo. Their regulation is complex enough to underlie the precision in filament dynamics needed by stimulated cells. Disassembly of actin by AC proteins is inhibited in vitro by phosphorylation of ser3 and pH<7.1. This study of Swiss 3T3 cells demonstrates that pH also affects AC behavior in vivo: (1) Wounded cells show pH-dependent AC translocation to alkaline-induced ruffling membrane; (2) The Triton extractable (soluble) ADF from Swiss 3T3 cells decreases from 42+/-4% to 23+/-4% when the intracellular pH (pH(i)) is reduced from 7.4 to 6.6; (3) Covariance and colocalization analyses of immunostained endogenous proteins show that ADF partitions more with monomeric actin and less with polymeric actin when pH(i) increases. However, the distribution of cofilin, a less pH-sensitive AC in vitro, does not change with pH; (4) Only the unphosphorylatable AC mutant (A3), when overexpressed as a GFP chimera, uniquely produces aberrant cellular phenotypes and only if the pH is shifted from 7.1 to 6.6 or 7.4. A mechanism is proposed that explains why AC(A3)-GFP and AC(wt)-GFP chimeras generate different phenotypes in response to pH changes. Phospho-AC levels increase with cell density, and in motile cells, phospho-AC increases with alkalization, suggesting a homeostatic mechanism that compensates for increased AC activity and filament turnover. These results show that the behavior of AC proteins with pH-sensitivity in vitro is affected by pH in vivo.

3T3 Cells↗

PubMed2000

Identification of nolR-regulated proteins in Sinorhizobium meliloti using proteome analysis.

Extractable proteins from Sinorhizobium meliloti strains AK631 and EK698 (a Tn5-induced noIR-deficient mutant of AK631), grown in tryptone agar (TA) medium with or without the addition of the plant signal luteolin, were separated by two-dimensional gel electrophoresis and compared. Analysis of silver-stained gels showed that the noIR mutant had 189 proteins that were significantly altered in their levels (101 protein spots up- and 88 downregulated). Coomassie-stained preparative two-dimensional (2-D) gels or polyvinylidene difluoride (PVDF) membranes blotted from preparative gels showed that at least 52 of the altered proteins could be reproducibly detected and isolated from the noIR mutant. These 52 altered protein spots were classified into five groups based on an assessment of protein abundance by computer analysis and the effect of the presence or absence of luteolin addition to the growth medium. N-terminal microsequencing of 38 proteins revealed that the most striking feature of the consequence of the noIR mutation is the number and broad spectrum of cellular functions that are affected by the loss of the NoIR function. These include proteins involved in the tricarboxylic acid (TCA) cycle, heat shock and cold shock proteins, protein synthesis, a translation elongation factor, oxidative stress and cell growth and maintenance functions. We propose that the NoIR repressor is a global regulatory protein which responds to environmental factors to fine-tune intracellular metabolism.

Bacterial Proteins↗

PubMed2000

Proteome analysis demonstrates complex replicon and luteolin interactions in pSyma-cured derivatives of Sinorhizobium meliloti strain 2011.

Sinorhizobium meliloti was studied by proteomic analysis to investigate the contribution made by plasmid-encoded functions on the intracellular regulation of this bacterium. Protein profiles of strain 2011 were compared with those from its mutant strains which were either cured of their pRme2011a (also called pSyma) plasmid (strain 818), or contained an extensive deletion of this plasmid (strain SmA146). Plasmid pSyma contains the nodulation and nitrogen fixation genes and is 1.4 Mbp with an estimated coding potential of 1,400 proteins. However, under the growth conditions used we could detect 60 differences between the parent strain and its pSyma-cured derivative, strain 818. While the majority of these differences were due to regulatory changes, such as up- and downregulation, some proteins were totally missing in some strains. These 60 proteins were classified into 21 subgroups, A to U, based on their measured protein levels when the cells were grown in the presence or absence of luteolin. Comparisons were made between the different strains to assess the possible interactions of the different proteins of the subgroups and plasmid pSyma. These results suggest that pSyma has a role in the regulation of the expression of genes from the other replicons (3.5 Mbp chromosome and the 1.7 Mbp pSymB plasmid) present in the S. meliloti cells. Proteome analysis provides a sensitive tool to examine the functional organisation of the S. meliloti genome and the intracellular gene interactions between replicons and will provide a powerful analytical tool to complement the genome sequencing of strain 1021.

Bacterial Proteins↗

PubMed2000

Modulation of myocardial SOD and iNOS during ischemia-reperfusion by antisense directed at ACE mRNA.

Renin-angiotensin system (RAS) is involved in the regulation of superoxide dismutase (SOD) and nitric oxide (NO) equilibrium, and its modulation protects hearts from ischemic dysfunction. We examined the effect of a new antisense-oligodeoxynucleotides (AS-ODNs) directed at ACE mRNA on SOD and iNOS expression during myocardial ischemia. Sprague-Dawley rats were treated with saline, AS-ODNs, or inverted-ODNs (IN-ODNs), given with liposome DOTAP/DOPE. Hearts were excised and subjected to 25 min of ischemia followed by 30 min of reperfusion. Ischemia-reperfusion in saline-treated hearts resulted in a decrease in the expression of SOD and an increase in the expression of inducible NOS (iNOS) genes concurrently with myocardial dysfunction. AS-ODNs, but not IN-ODNs, protected hearts against functional deterioration, and upregulated SOD expression and inhibited the expression of iNOS. ACE protein expression was decreased in the rat hearts of the AS-ODNs-treated group, but not in the IN-ODNs group. Thus manipulation of RAS with AS-ODNs directed at ACE mRNA can ameliorate cardiac dysfunction and modulate expression of SOD and iNOS at genomic level.

Animals↗

PubMed2000

Thermotolerance preserves endothelial vasomotor function during ischemia/reperfusion.

Ischemia/reperfusion (I/R) results in endothelial dysfunction, seen as loss of endothelium-dependent vasodilatation. In prolonged ischemia, this can result in marked vasospasm or no reflow in the microvasculature. Thermotolerance (T) attenuates I/R-induced microvascular injury. The aim of this study was to investigate the effect of thermotolerance on I/R-induced vasomotor changes and "no reflow." Sprague-Dawley rats were randomized into an ischemia/reperfusion group (I/R group) and a group in which thermotolerance (41 + 0.5 degrees C for 15 min 18 h prior to I/R) was induced (T + I/R group). IR injury was established by occlusion of the superior mesenteric and celiac vascular pedicle for 30 min, followed by 60 min of reperfusion. Vasomotor function [arteriolar constriction:dilatation (C:D) ratio] measured by response to acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) and "no-reflow" phenomenon were determined in mesenteric arterioles by intravital microscopy. Data are expressed as means +/- SEM and were analyzed using ANOVA and chi(2) test. I/R caused a significant decrease in endothelium-dependent vasodilatation (C:D = 1.37+/-0.31 in IR group vs. 2.06+/-0.20 in baseline, P<0.01) and no reflow in arterioles in 16 of 28 unheated rats. Endothelium-independent dilatation was not altered by I/R. Thermotolerance attenuated this impairment of endothelium-dependent dilatation (P<0.01 vs. IR; C:D = 1.95+/-0.19) and reduced no-reflow phenomenon to 4 of 16 rats (P<0.05 vs. IR). This study demonstrated that thermotolerance preserves endothelial vasomotor function and markedly reduces "no reflow" in arterioles.

Animals↗

PubMed2000

The role of neutrophil activation in pathogenesis of preeclampsia.

To investigate the effect of neutrophil activation on pathogenesis of pre-eclampsia, neutrophil activation was examined by using flow cytometry to assess the CD11b expression and the levels of plasma endothelin-1 (ET-1) and serum NO2- were also measured by using non-equilibrium radioimmunoassay and by Griess assay in 29 pregnant women with pre-eclampsia and 31 normal pregnant women at third trimester. The expression of neutrophil CD11b was significantly elevated in women with pre-eclampsia as compared with that of normal pregnant women at third trimester. The mean fluorescence index of CD11b was 438.38 +/- 179.91 and 326.97 +/- 170.14 respectively (P < 0.05). The plasma ET-1 level and serum NO2- concentration in pre-eclampsic women (63.69 +/- 48.33 pg/ml and 20.03 +/- 4.77 mumol/L, respectively) were both significantly increased as compared with those in the normal pregnancy women (29.98 +/- 20.25 pg/ml and 15.47 +/- 5.47 mumol/L, respectively, P < 0.01). The neutrophil CD11b expression was significantly elevated in pre-eclampsia. The increased neutrophil activation may cause the damage of vascular endothelium and result in NO release compensatory increase in endothelial cells, suggesting that the neutrophil activation may play a key role in pathogenesis of pre-eclampsia.

Adult↗

PubMed2000

Flow injection spectrophotometric determination of anionic surfactants using methyl orange as chromogenic reagent.

A flow injection(FI) spectrophotometric method for the determination of anionic surfactants was developed on the basis of the competition for the cationic surfactant cetyl pyridine (CP+) chloride between the acidic dye methyl orange (MO) and anionic surfactants. In a pH 5.0 medium the cation of cetyl pyridine (CP+) reacts with dissociated methyl orange (MO-) to form an ion-associate complex, causing a blue shift of lambda(max) from 465 nm for MO- to 358 nm for the CP+ x MO- associate. The MO- in the ion-associate complex can be quantitatively substituted by such anionic surfactants as sodium dodecyl benzene sulfonate (DBS) or sodium lauryl sulfate (LS), leading to an increase in the absorbance measured at 465 nm. This increased absorbance value is proportional to the concentration of anionic surfactants. Various chemical and physical parameters for the FI spectrophotometric method were optimized, and interference-free levels were examined. At the optimized conditions, Beer's law was obeyed in the range 1.4 approximately 25 mg/L sodium DBS for an injected sample volume of 180 microL, and a detection limit of 0.22 mg/L for sodium DBS was achieved at a sampling rate of 90 h(-1). Eleven determinations of a 16 mg/L sodium DBS solution gave a RSD of 0.4%. The proposed method has successfully been applied to the determination of anionic surfactant concentration in waste water and in detergents.

Anions↗

PubMed2000

Diverse endogenous light chains contribute to basement membrane reactivity in nonautoimmune mice transgenic for an anti-laminin Ig heavy chain.

Basement membrane proteins are targeted in a variety of pathologic autoimmune responses, yet little is known regarding the origins and regulation of this subset of pathogenic lymphocytes. To examine the generation and fate of B cells reactive with a matrix autoantigen, nonautoimmune C57BL/6 mice were rendered transgenic for a nephrotropic lupus anti-laminin immunoglobulin (Ig) H chain, termed LamH-Cmu. We previously reported recovery of two distinct phenotypes among LamH-Cmu-transgenic mice: progeny of founders M6 and M29 contained abundant transgene-expressing B cells but little anti-laminin Ig, whereas spontaneous autoreactivity was readily recovered from the M7 lineage that expressed minimal B-cell mIgM. To explore the spectrum of autoreactivity generated in vivo by different LamH-Cmu-endogenous L-chain combinations, we determined in vitro and in vivo antigen reactivity and L-chain V-region sequences of 17 LamH-Cmu-transgenic anti-laminin Igs. The results reveal a heterogeneous population of anti-laminin Igs with different fine specificities encoded by diverse endogenous L chains, encompassing nine different Vk gene families, 11 Vk genes, and three Jk genes. Many of the L chains are identical to known or putative unmutated germline Vk genes used to encode Igs reactive with self and foreign antigens in nonautoimmune and genetically autoimmune-prone mouse strains. These observations confirm that the LamH-Cmu H chain plays a dominant role in determining anti-laminin reactivity, and indicate that nonautoimmune B6 mice are fully capable of generating a diverse pool of basement-membrane-reactive B cells using unmutated Ig genes. When interpreted in the context of the divergent M6/M29 and M7 transgenic mouse phenotypes, our findings further suggest that these matrix-reactive lymphocytes are not spontaneously activated in vivo under normal circumstances.

Amino Acid Sequence↗

PubMed2000

Induction of oocyte maturation by jun-N-terminal kinase (JNK) on the oncogenic ras-p21 pathway is dependent on the raf-MEK signal transduction pathway.

PURPOSE: We have previously found that microinjection of activated MEK (mitogen activated kinase kinase) and ERK (mitogen-activated protein; MAP kinase) fails to induce oocyte maturation, but that maturation, induced by oncogenic ras-p21 and insulin-activated cell ras-p21, is blocked by peptides from the ras-binding domain of raf. We also found that jun kinase (JNK), on the stress-activated protein (SAP) pathway, which is critical to the oncogenic ras-p21 signal transduction pathway, is a strong inducer of oocyte maturation. Our purpose in this study was to determine the role of the raf-MEK-MAP kinase pathway in oocyte maturation and how it interacts with JNK from the SAP pathway. METHODS: We microinjected raf dominant negative mutant mRNA (DN-raf) and the MEK-specific phosphatase, MKP-T4, either together with oncogenic p21 or c-raf mRNA, into oocytes or into oocytes incubated with insulin to determine the effects of these raf-MEK-MAP kinase pathway inhibitors. RESULTS: We found that oocyte maturation induced by both oncogenic and activated normal p21 is inhibited by both DN-raf and by MKP-T4. The latter more strongly blocks the oncogenic pathway. Also an mRNA encoding a constitutively activated MEK strongly induces oocyte maturation that is not inhibited by DN-raf or by MKP-T4. Surprisingly, we found that oocyte maturation induced by JNK is blocked both by DN-raf and MKP-T4. Furthermore, we discovered that c-raf induces oocyte maturation that is inhibited by glutathione-S-transferase (GST), which we have found to be a potent and selective inhibitor of JNK. CONCLUSION: We conclude that there is a strong reciprocal interaction between the SAP pathway involving JNK and the raf-MEK-MAP kinase pathway and that oncogenic ras-p21 can be preferentially inhibited by MEK inhibitors. The results imply that blockade of both MEK and JNK-oncogenic ras-p21 interactions may constitute selective synergistic combination chemotherapy against oncogenic ras-induced tumors.

Animals↗

PubMed2000

Modulation of cloned skeletal muscle sodium channels by the scorpion toxins Lqh II, Lqh III, and Lqh alphaIT.

The scorpion alpha-toxins Lqh II, Lqh III, and Lqh alphaIT from Leiurus quinquestriatus hebraeus are representatives of typical alpha-toxins, specific for either mammals (Lqh II) or insects (Lqh alphaIT), and alpha-like toxins (Lqh III) which act on both mammals and insects. For a comparative study of the effects of these toxins on mammalian sodium channels we stably expressed rat skeletal muscle sodium channel alpha subunits (microI) in HEK 293 cells and measured Na+ currents in the whole-cell patch-clamp mode. The alpha- and alpha-like toxins strongly slowed down channel inactivation with a half-maximal effect at 1.4 nM (Lqh II), 5.4 nM (Lqh III), and 0.5 nM (Lqh alphaIT). The recovery from fast inactivation was accelerated by all toxins with the potency sequence: Lqh II>Lqh alphaIT>Lqh III. The voltage dependence of inactivation and recovery from inactivation were reduced while the threshold for activation was only slightly shifted by approximately equal to 10 mV without altering the slope factors, suggesting uncoupling of the impaired inactivation from the activation. The toxins induced an increase in peak inward current, which was accounted for by an increased maximal open-channel probability. Although all three toxins induced similar modifications of the channel properties, their kinetics of association and dissociation were very different. Between -140 and -80 mV toxin association was not voltage dependent. In 100 nM toxin the association time constants were: 1.3 s (Lqh II), 20 s (Lqh III), and 3.8 s (Lqh alphaIT). At positive voltages the toxin dissociated from the channel; at +100 mV the dissociation time constants were 30, 321, and 135 ms, respectively. In contrast to the association, dissociation was voltage dependent with a similar slope of about 12 mV per e-fold change for all three toxins. The strong differences in the association and dissociation kinetics of these toxins may identify them as members of different scorpion alpha-toxin subgroups.

Animals↗

PubMed2000

Genomic structure of a copy of the human TPTE gene which encompasses 87 kb on the short arm of chromosome 21.

The testis-expressed human TPTE is a putative transmembrane tyrosine phosphatase, probably involved in signal transduction pathways of the endocrine and/or the spermatogenetic function of the testis. TPTE was mapped to the pericentromeric region of human chromosomes 21 and 13, and to chromosomes 15, 22, and Y. It is unknown which of the TPTE copies are transcribed, contain intronic sequences, and/or have open reading frames. Here, in silico analysis of the genomic sequence of human chromosome 21 allowed the determination of the genomic structure of a copy of the TPTE gene. This copy consists of 24 exons and spans approximately 87 kb. The mapping position of this copy of TPTE on the short arm of chromosome 21 was confirmed by FISH using the BAC 15L0C0 clone as a probe that contains almost the entire TPTE gene. This is the first description of the genomic sequence of a non-RNR gene on the short arm of human acrocentric chromosomes.

Chromosome Mapping↗

PubMed2000

Thrombospondin-2 gene expression and protein localization during embryonic mouse palate development.

The mammalian palate develops from projections of the paired maxillary processes termed palatal shelves. Shelf growth is an essential in normal palatal morphogenesis. Mesenchymal proliferation in the palatal shelves is modulated by transforming growth factor-1 (TGF-1), among other growth factors. Several pathways effect TGF-beta activation, including one which utilizes thrombospondin (TSP). TSP-1 is a major activator of TGF-beta in vivo and has been localized in head mesenchyme, including palates. TSP-2 appears to inhibit TSP-1 activation of latent TGF-beta by competitively binding the latent TGF-beta. Here the TSP-2 mRNA transcript and the immunolocalization of TSP-2 protein with progressive palatogenesis were quantified. There was a significant (p < 0.05) decline of TSP-2 transcript with palatal maturation; there was no evidence correlating the TSP-2 transcription with the amount of activated TGF-beta. At the vertical shelf stage of palatogenesis, TSP-2 protein was found throughout the extracellular matrix of shelf mesenchyme. By the horizontal shelf stage, TSP-2 protein was principally localized to the ossification centres of the developing maxilla, both in extracellular matrix and bone; far less was seen in palatal shelves proper. These results suggest that TSP-2 is multifunctional during embryonic palate formation.

Animals↗

PubMed2000

Knowledge about human papillomavirus among adolescents.

OBJECTIVE: To assess knowledge of human papillomavirus (HPV) among high school-aged adolescents. METHODS: We administered written surveys to 523 inner-city high school students in Toronto, Canada, that asked about HPV, other sexually transmitted diseases (STDs), and Papanicolaou testing. We also asked them to report doctor or clinic visits and whether they received sexual health information at those visits. The predictor variables used in analysis were gender and sexual experience. RESULTS: Eighty-seven percent of our population [95% confidence interval (CI) 84%, 89%) had not heard of HPV. Although adolescent women were more knowledgeable about Papanicolaou testing than adolescent men, only 39% of sexually experienced adolescent women knew who should get a Papanicolaou test. Sexually experienced and inexperienced adolescents failed to identify correctly their STD risk. Both genders showed greater knowledge about human immunodeficiency virus (HIV) than other diseases. Among adolescent women, 85% had visited a doctor or clinic within the past year, but only 29% had talked about sexual health. CONCLUSION: Knowledge of HPV infection and cervical cancer screening was low in this urban adolescent population. Improved efforts are needed for prevention of HPV infection and HPV-related cervical changes. Programs modeled after HIV-education programs might be effective. Doctors' offices and clinics providing health care to adolescents should take greater responsibility in sexual health education.

Adolescent↗

PubMed2000

The acute and subchronic toxicity of BRB-I-28, a novel class Ib antiarrhythmic agent, in CD-1 mice.

The acute and subchronic toxic effects of BRB-I-28 (7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane HCl), a novel class Ib antiarrhythmic agent, were investigated in male and female mice. The estimated oral LD(50) for BRB-I-28 was 128 mg/kg (male mice) and 131 mg/kg (female mice). In subchronic oral studies, four groups of mice (15/sex/group/dose) were fed daily with diets containing BRB-I-28 for 90 consecutive days. The equivalent daily doses were approximately 0, 16, 32, 76 (male) and 0, 18, 37, 89 mg/kg (female). All mice survived. Food consumption per day was decreased, but water consumption per day was increased (in a non-dose-dependent manner). However, both mean body weight and mean body weight gain were not significantly changed as were true for hematological and clinical chemistry profiles, except for serum Na(+) concentration (male) and serum K(+) concentration in male and female mice (high dose levels). Hepatocellular necrosis occurred in male and female mice (in a dose-dependent fashion). Renal cortical vacuoles and myocardial necrosis with low numbers of lymphocytic infiltrations were present in female mice (middle and high doses). Lesions in the liver, kidney and heart were mild with (very small) changes in serum biochemical values. These data suggest that BRB-I-28 has limited toxic potential, and coupled with low proarrhythmic and other desirable cardiovascular effects, makes BRB-I-28 worthy of further development.

Animals↗

PubMed2000

Fetal renal volume in normal gestation: a three-dimensional ultrasound study.

To establish a reference chart of fetal kidneys in normal pregnancy, we performed a prospective and cross-sectional study. A total of 152 singleton fetuses ranging between 20 and 40 weeks' gestation and meeting the criteria of normal pregnancies were included. Three-dimensional ultrasound (3-D US) was used to measure the fetal renal volume. Our results revealed that both renal volumes are highly correlated with the fetal gestational age. Using gestational age (GA) as the independent variable and right renal volume (RRV) as the dependent variable, the best-fit regression equation was RRV (mL)=0.74053xGA (week)-13.318 (r = 0.89, p < 0.001). Similarly, the best-fit equation for the left renal volume (LRV) was LRV (mL)=0. 76093xGA (week)-13.421 (r = 0.86, p < 0.001). The normal growth centiles of both kidneys were established based on these two equations. There were no significant differences of the volumes between bilateral kidneys. In conclusion, our data of fetal renal volumes assessed by 3-D US may serve as a reference in evaluating fetal renal growth.

Cross-Sectional Studies↗

PubMed2000

Determination of loperamide in rat plasma and bovine serum albumin by LC.

A rapid, isocratic liquid chromatographic (LC) method was developed for the determination of loperamide (Lop) in solutions of bovine serum albumin (BSA) and rat plasma. Prior to LC analysis, BSA solutions or rat plasma samples were treated with metaphosphoric acid to precipitate protein. Supernatant was directly injected onto a C18 reverse phase column and loperamide was monitored by a UV detector set at 195 nm. The concentrations of Lop in both rat plasma and BSA solution samples were determined by comparison with their calibration curves, which were generated from the peak area ratio of Lop to internal standard, clomipramine versus loperamide concentration. The calibration curves were linear in the range 0-3.0 microg ml(-1) of Lop for the BSA solution sample and 0-1.0 microg ml(-1)for the rat plasma sample. Overall recoveries of loperamide added to BSA and rat plasma samples were 101.4 and 95.5%, respectively. The method is simple (no extraction), rapid (22 min separation time), sensitive (the detection limit of loperamide is 50 ng ml(-1) for the BSA solution sample and 100 ng ml(-1) for the rat plasma sample), reproducible (within-day R.S.D. of 2.59-7.11%, among-day R.S.D. of 1.25-5.97%), and suitable for routine analysis of loperamide in rat plasma and BSA solution samples.

Animals↗

PubMed2000

The family caregiver of the older cancer patient.

Cancer care is becoming increasingly complex. The health care practices of the present day make it imperative that the family provide assistance in the day-to-day management of a patient's symptoms and in the implementation of home care. This increased responsibility for the family caregiver can come at great cost to the overall functioning of the family, because of role changes, changes in the family structure, and financial stressors, among others. Caregivers can experience adverse effects on their mental and physical health that can remain long after the caregiving role has ended. Although much of the research has focused on the negative elements of caregiving, it must be remembered that there are positive aspects to caregiving, which are now receiving attention in the research literature. Although other factors affect caregiving, the model of factors important in the caregiving experience presented in this article may provide the impetus for studying the relationships among these different factors. Results of these studies will allow the development of specific interventions to help caregivers be more effective in their caregiving role and, at the same time, address the overall impact of caregiving on the family.

Aged↗

PubMed2000

Neuropilin-2 regulates the development of selective cranial and sensory nerves and hippocampal mossy fiber projections.

Neuropilin-1 and neuropilin-2 bind differentially to different class 3 semaphorins and are thought to provide the ligand-binding moieties in receptor complexes mediating repulsive responses to these semaphorins. Here, we have studied the function of neuropilin-2 through analysis of a neuropilin-2 mutant mouse, which is viable and fertile. Repulsive responses of sympathetic and hippocampal neurons to Sema3F but not to Sema3A are abolished in the mutant. Marked defects are observed in the development of several cranial nerves, in the initial central projections of spinal sensory axons, and in the anterior commissure, habenulo-interpeduncular tract, and the projections of hippocampal mossyfiber axons in the infrapyramidal bundle. Our results show that neuropilin-2 is an essential component of the Sema3F receptor and identify key roles for neuropilin-2 in axon guidance in the PNS and CNS.

Animals↗