Identification of KASP markers and putative genes for pre-harvest sprouting resistance in common wheat(Triticum aestivum L.)

Common wheat(Triticum aestivum L.)is the most important crop in the world and a typical allopolyploid with a large and complex genome.Pre-harvest sprouting(PHS)leads to a significant reduction in grain quality worldwide.PHS is a complex trait with related QTL located on different chromosomes.However,the study of markers and genes related to PHS resistance is limited especially for whitegrained wheat.Four pairs of near isogenic lines(NILs)from a white-grained wheat cross of Chara
DM5637B*8 targeting a major QTL for PHS resistance(Qphs.ccsu-3A.1)on wheat chromosme 3AL were genotyped using the 90K SNP Illumina iSelect array.Ten SNPs were identified,with a 75%-100%consistency between genotype and phenotype in the resistant or susceptible isolines.The 10 SNPs were converted to cost-effective kompetitive allele-specific PCR(KASP)markers.Screening of 48 wheat cultivars with different phenotypes of PHS identified four KASP markers with 81.3%-85.4%conformity between genotype and phenotype.Further investigation revealed that the four SNPs(BS00022245_51,Kukri_c49927_151,BS00022884_51 and BS00110550_51)corresponding to the four validated KASP markers are residing in three independent genes(TraesCS3A03G1072800,TraesCS3A03G1072400,TraesCS3A03G1071800)close to each other with a distance of 4.28-4.48 Mb to the targeted QTL.These three annotated genes have potential functions related to PHS resistance.Our study revealed that combined use of NILs and the 90K SNP chip is a powerful approach for developing KASP markers and mining functional genes in wheat.The KASP markers for PHS resistance on chromosome 3AL are useful for high-throughput evaluation and marker-assisted selection,and the three identified genes could lead to a better understanding of the genetic pathways controlling PHS.

QTL mapping for pre-harvest sprouting in a recombinant inbred line population of elite wheat varieties Zhongmai 578 and Jimai 22

Pre-harvest sprouting(PHS)is one of the serious global issues in wheat production.Identification of quantitative trait loci(QTL)and closely-linked markers is greatly helpful for wheat improvement.In the present study,a recombinant inbred line(RIL)population derived from the cross of Zhongmai 578(ZM578)/Jimai 22(JM22)and parents were phenotyped in five environments and genotyped by the wheat 50 K single-nucleotide polymorphism(SNP)array.Two QTL of germination index(GI),QGI.caas-3A and QGI.caas-5A,were detected,explaining 4.33%–5.58%and 4.43%–8.02%of the phenotypic variances,respectively.The resistant effect of QGI.caas-3A was contributed by JM22,whereas that of QGI.caas.5A was from ZM578.The two QTL did not correspond to any previously identified genes or genetic loci for PHSrelated traits according to their locations in the Chinese Spring reference genome,indicating that they are likely to be new loci for PHS resistance.Four kompetitive allele-specific PCR(KASP)markers K_AX-109605367and K_AX-179559687 flanking QGI.caas-3A,and K_AX-111258240 and K_AX-109402944flanking QGI.caas-5A,were developed and validated in a natural population of 100 wheat cultivars.The distribution frequency of resistance alleles at Qphs.caas-3A and Qphs.caas-5A loci were 82.7%and57.1%,respectively,in the natural population.These findings provide new QTL and tightly linked KASP markers for improvement of PHS resistance in wheat.

Evaluation of Pre-Harvest Sprouting(PHS)Resistance and Screening of High-Quality Varieties from Thirty-Seven Quinoa(Chenopodium quinoa Willd.)Resources in Chengdu Plain

Pre-harvest sprouting(PHS)will have a serious effect both on the yield and quality of quinoa(Chenopodium quinoaWilld.).It is crucial to select and breed quinoa varieties with PHS resistance and excellent agronomic traits for guidance production and utilization of quinoa.A comprehensive evaluation of the PHS resistance and agronomic traits of 37 species of quinoa resources was conducted in Chengdu Plain.The evaluation used various methods,including grain germination rate(GR),grain germination index(GI),total spike germination rate(SR),total grain germination index(SI),grey correlation analysis(GCA),cluster analysis and correlation analysis.Results showed significant differences in PHS resistance and agronomic traits amongst the 37 quinoa resources.CDU-23 was most resistant to PHS within 24 h,with a germination rate of 2.67%and 0%according to the GR and SR results,respectively.However,in the same time,CDU-31 showed the maximum susceptibility to PHS based on the SR of 31.07%,while CDU-34 was the most sensitive to PHS according to the GR of 100%.The comprehensive evaluation identified one and nine kinds of high resistance species for grain and whole spike germination,respectively.In both cases,the coefficients of variation(CV)for these parameters were 34.78%and 82.13%,respectively.GCA results showed that the magnitude of the association between each trait and yield in the thirty-seven quinoa resources was in the following order:thousand grain weight>seed length>seed area>seed width.Although the seed weight of CDU-18 reached 3.7010 g,the seed weight of CDU-5 was only 1.6030 g.However,the size of the seeds,their width and area did not correlate with their 1000-grain weight.There was a complex correlation between PHS resistance index and agronomic traits.Based on clustering analysis,thirty-seven quinoa resources were classified into three taxa.It was found that various taxa differed in PHS resistance and agronomic traits.Several comparisons of the aggregated data led to the selection of five varieties of quinoa,of which CDU-2 presented excellent agronomic qualities and strong PHS resistance.This study has provided a reference for breeding excellent quinoa varieties with PHS resistance.

QTL mapping revealed TaVp-1A conferred pre-harvest sprouting resistance in wheat population Yanda 1817×Beinong 6

Pre-harvest sprouting （PHS） occurs frequently in most of the wheat cultivation area worldwide, which severely reduces yield and end-use quality, resulting in substantial economic loss. In this study, quantitative trait loci （QTL） for PHS resistance were mapped using an available high-density single nucleotide polymorphism （SNP） and simple sequence repeat （SSR） genetic linkage map developed from a 269 recombinant inbred lines （RILs） population of Yanda 1817xBeinong 6. Using phenotypic data on two locations （Beijing and Shijiazhuang, China） in two years （2012 and 2013 harvesting seasons）, five QTLs, designated as QPhs.cau-3A. 1, QPhs.cau-3A.2, QPhs.cau-5B, QPhs.cau-4A, and QPhs.cau-6A, for PHS （GP） were detected by inclusive composite interval mapping （ICIM） （LOD≥2.5）. Two major QTLs, QPhs.cau-3A.2 and QPhs.cau-5B, were mapped on 3AL and 5BS chromosome arms, explaining 6.29-21.65% and 4.36-5.94% of the phenotypic variance, respectively. Precise mapping and comparative genomic analysis revealed that the TaVp-1A flanking region on 3AL is responsible for QPhs.cau-3A.2. SNP markers flanking QPhs.cau-3A.2 genomic region were developed and could be used for introgression of PHS tolerance into high yielding wheat varieties through marker-assisted selection （MAS）.

Isolation and Functional Characterization of a B3 Transcription Factor Gene <i>FUSCA3</i>Involved in Pre-Harvest Sprouting Resistance in Wheat

Pre-harvest sprouting (PHS) reduces yields and grain quality, resulting in seriously economic losses in wheat. It has been showed that PHS is significantly correlated to seed dormancy levels. FUSCA3 (FUS3) gene is considered to be the key regulator of seed dormancy. However, little information is available about the function of FUS3 gene (TaFUS3) in wheat. In this study, three homologous genes were identified in wheat grain, and their functions were investigated by gene silencing. Three full-length DNA (3477, 3534 and 3501 bp) and cDNA (1015, 1012 and 1015 bp) sequences encoding a B3 transcription factor, designated TaFUS3-3A, TaFUS3-3B and TaFUS3-3D, were first isolated from common wheat. The transcription of three TaFUS3 genes in seed development and germination process was detected. TaFUS3-3B and TaFUS3-3D had similar expression profiles, and high levels of gene transcripts were detected in seeds at 25 DAP (days after pollination) and after 24 h of imbibition. However, the transcription of TaFUS3-3A was not detected. Silencing of TaFUS3 in common wheat spikes resulted in increased seed germination and PHS. Compared with wild-type, the TaFUS3-silenced plants showed increased expression of genes related to GA biosynthesis and ABA metabolism, and decreased expression of genes associated with ABA biosynthesis. Moreover, silencing of TaFUS3 in wheat plants led to a decrease in embryo sensitivity to ABA and changed the expression of genes involved in ABA signal transduction. The results of gene silencing indicated that TaFUS3 plays a positive role in wheat seed dormancy and PHS-resistance, which might be associated with ABA, GA level and signal transduction.

The association between the allelic state of <i>Vp</i>-1<i>B</i>and pre-harvest sprouting tolerance in red-seeded hexaploid triticale

The core collection of red-seeded winter hexaploid triticale with different pre-harvest sprouting (PHS) resistance has been evaluated for the allelic structure of the gene VIVIPAROUS-1B (Vp-1B) with STS molecular marker. The discovered structure of the collection was as follows: 50.0% and 41.7% of the collection carries Vp-1Bа and Vp-1Bc alleles, respectively, while 8,3% possesses both of them. As a result of the seed color estimation, the collection has been divided into two groups: with dark red seeds and light red seeds. The allele Vp-1Bc has appeared to be associated with PHS resistance while Vp-1Ba with PHS susceptibility in the triticale accessions with light red seeds only. The influence of the seed color and allelic state of Vp-1B on PHS resistance in triticale is discussed.

TaSRO1 interacts with TaVP1 to modulate seed dormancy and pre-harvest sprouting resistance in wheat

Dormancy is an adaptive trait which prevents seeds from germinating under unfavorable environmental conditions.Seeds with weak dormancy undergo pre-harvest sprouting(PHS)which decreases grain yield and quality.Understanding the genetic mechanisms that regulate seed dormancy and resistance to PHS is crucial for ensuring global food security.In this study,we illustrated the function and molecular mechanism of TaSRO1 in the regulation of seed dormancy and PHS resistance by suppressing TaVP1.The tasro1 mutants exhibited strong seed dormancy and enhanced resistance to PHS,whereas the mutants of tavp1 displayed weak dormancy.Genetic evidence has shown that TaVP1 is epistatic to TaSRO1.Biochemical evidence has shown that TaSRO1 interacts with TaVP1 and represses the transcriptional activation of the PHS resistance genes TaPHS1 and TaSdr.Furthermore,TaSRO1 undermines the synergistic activation of TaVP1 and TaABI5 in PHS resistance genes.Finally,we highlight the great potential of tasro1 alleles for breeding elite wheat cultivars that are resistant to PHS.

Sdr4 dominates pre-harvest sprouting and facilitates adaptation to local climatic condition in Asian cultivated rice

Pre-harvest sprouting(PHS),which reduces grain yield and quality,is controlled by seed dormancy genes.Because few dormancy-related genes have been cloned,the genetic basis of seed dormancy in rice(Oryza sativa L.)remains unclear.Here,we performed a genome-wide association study and linkage mapping to dissect the genetic basis of seed dormancy in rice.Our findings suggest that Seed Dormancy4(Sdr4),a central modulator of seed dormancy,integrates the abscisic acid and gibberellic acid signaling pathways at the transcriptional level.Haplotype analysis revealed that three Sdr4 alleles in rice cultivars already existed in ancestral Oryza rufipogon accessions.Furthermore,like the semi-dwarf 1(SD1)and Rc loci,Sdr4 underwent selection during the domestication and improvement of Asian cultivated rice.The distribution frequency of the Sdr4-n allele in different locations in Asia is negatively associated with local annual temperature and precipitation.Finally,we developed functional molecular markers for Sdr4,SD1,and Rc for use in molecular breeding.Our results provide clues about the molecular basis of Sdr4-regulated seed dormancy.Moreover,these findings provide guidance for utilizing the favorable alleles of Sdr4 and Rc to synergistically boost PHS resistance,yield,and quality in modern rice varieties.

Breeding for pre-harvest sprouting resistance in bread wheat under rainfed conditions

Pre-harvest sprouting in wheat is the germination of seeds within the spikes when rains occur after or during grain ripening, which occurs commonly in the barani tract of Pakistan. Therefore, 10 cultivars and five advanced lines of spring bread wheat were evaluated for pre-harvest sprouting resistance. After natural rainfall,seeds were immediately collected from the wet spikes and tested for germinating ability. Three different germination tests were applied to hand-threshed seed:(1) spikes threshed on the day of sampling and germination tested immediately,(2) spikes threshed on the day of sampling and germination tested 1 week later, and(3) spikes threshed 1 week after sampling and germination test immediately after threshing. Seeds and spikes kept for 1 week were place on blotting paper at room temperature.Cultivars BARS-09, 09 FJ17, Doukkala-12, NARC-09 and Ouassou-20 exhibited higher sprouting resistance while other genotypes were susceptible to pre-harvest sprouting in each of the three tests. A diallel crossing was conducted with six susceptible and two resistant genotypes to assess the genetic behavior of pre-harvest sprouting resistance.The combining ability(CA) demonstrated a higher proportion of additive genetic effects for sprouting resistance, because of higher variance of general and specific CA for both parameters under study. Doukkala-12 and BARS-09 showed increased pre-harvest sprouting resistance in their F1 descendants.

Regulation of the growth of sprouting roots of black locust seedlings using root barrier panels

How can we regulate an invasive alien species of high commercial value?Black locust(Robinia pseudoacacia L.)has a unique capacity for seed dispersal and high germination.Field surveys indicate that black locust increases its growing area with sprouting roots and the elongation of horizontal roots at a soil depth of 10 cm.Therefore,a method to regulate the development of horizontal roots could be eff ective in slowing the invasiveness of black locust.In this study,root barrier panels were tested to inhibit the growth of horizontal roots.Since it is labor intensive to observe the growth of roots in the fi eld,it was investigated in a nursery setting.The decrease in secondary fl ush,an increase in yellowed leafl ets,and the height in the seedlings were measured.Installing root barrier panels to a depth of 30 cm eff ectively inhibit the growth of horizontal roots of young black locust.

CsABF3-activated CsSUT1 pathway is implicated in pre-harvest water deficit inducing sucrose accumulation in citrus fruit

Pre-harvest water deficit(PHWD)plays an important role in sugar accumulation of citrus fruit.However,the mechanism is not known well.Here,it was confirmed that PHWD promoted sucrose accumulation of citrus fruit,but had limited effect on fructose,glucose and total acid.A sucrose transporter,Cs SUT1,which localizes to the plasma membrane,was demonstrated to function in sucrose transport induced by PHWD.Compared to wild-type,Cs SUT1 overexpression in citrus calli stimulated sucrose,fructose and glucose accumulation,while its silencing in juice sacs reduced sucrose accumulation.Increased sugar accumulation in transgenic lines enhanced plant drought tolerance,and resulted in decreased electrolyte leakage,malondialdehyde and hydrogen peroxide contents,as well as increased superoxide dismutase activity and proline contents.An abscisic acid(ABA)-responsive transcription factor,Cs ABF3,was found with a same expression pattern with Cs SUT1 under PHWD.Yeast one-hybrid,electrophoretic mobility shift assay and dual-luciferase assays all revealed that Cs ABF3 directly bound with the Cs SUT1 promoter by ABA responsive elements.When Cs ABF3 was overexpressed in citrus calli,the sucrose,fructose and glucose concentration increased correspondingly.Further,transgenic studies demonstrated that Cs ABF3 could affect sucrose accumulation by regulating Cs SUT1.Overall,this study revealed a regulation of Cs ABF3 promoting Cs SUT1 expression and sucrose accumulation in response to PHWD.Our results provide a detail insight into the quality formation of citrus fruit.

Comparative study of the effects of Tartary buckwheat seed and sprout consumption on the physiological indices and gut microbiota of C57BL/6J mice

Tartary buckwheat(Fagopyrum tataricum)is a well-known pseudocereal for its health and economic value.However,abundant antinutritional factors(ANFs)reduces its health benefits.As reported,germination can improve the nutritional profile of grains.In this study,we systematically evaluate the safety of Tartary buckwheat seeds(TB)and Tartary buckwheat sprouts(TBS)used as high active ingredients.After evaluating nutrition levels,bioactive compounds and ANFs in TBS during germinating,5^(th)-day TBS were selected as the raw material.C57BL/6J mice were gavaged daily with distilled water,TB,or TBS for 6 weeks.The physiological indices related to ANFs were determined.Results showed that the TB intake tends to generate negative effects on the gut microbiota,and organs.Additionally,upon TB intake,the Fe^(3+)content in serum,trypsin activity in pancreas and jejunum decreased,while the cytokine,IgE,and histamine levels in serum,water content in faeces,cytokine levels in liver and jejunum increased.Conversely,TBS did not induce any obvious negative effects on the above relevant indices and showed better lipid-lowering effect.Altogether,TBS are safer and more effective as a raw material to produce the functional food for long-term consumption with the intention of preventing and treating hyperlipidaemia.

Transcriptomics integrated with metabolomics reveals the mechanism of CaCl_(2)-HCl electrolyzed water-induced glucosinolate biosynthesis in broccoli sprouts

Glucosinolates are important phytochemicals in Brassicaceae.We investigated the effect of CaCl_(2)-HCl electrolyzed water(CHEW)on glucosinolates biosynthesis in broccoli sprouts.The results showed that CHEW treatment significantly decreased reactive oxygen species(ROS)and malondialdeh yde(MDA)contents in broccoli sprouts.On the the 8^(th)day,compared to tap water treatment,the the total glucosinolate content of broccoli sprouts with CHEW treatment increased by 10.6%and calcium content was dramatically enhanced from 14.4 mg/g DW to 22.7 mg/g DW.Comparative transcriptome and metabolome analyses revealed that CHEW treatment activated ROS and calcium signaling transduction pathways in broccoli sprouts and they interacted through MAPK cascades.Besides,CHEW treatment not only promoted the biosynthesis of amino acids,but also enhanced the expression of structural genes in glucosinolate synthesis through transcription factors(MYBs,bHLHs,WRKYs,etc.).The results of this study provided new insights into the regulatory network of glucosinolates biosynthesis in broccoli sprouts under CHEW treatment.

Tolerant Mechanism and Chromosome Location of Gene Controlling Sprouting Tolerance in Aegilops Tauschii Cosson

An artificial amphiploid RSP (2n = 42, AABBDD) between tetraploid landrace Ailanmai (Triticum turgidum L., 2n= 28, AABB) and Aegllops tauschii (DD, 2n = 14) expressed high tolerance to preharvest sprouting which derived from Ae. tauschii. Tolerance to preharvest sprouting of RSP was examined by four ways in six varying periods after anthesis. The germination percentages of preharvest intact spikes were only 6.06% in its high peak period of germination. Its tolerance was mainly decided by the seed dormancy. It was showed that the tolerance to sprouting in ' RSP' derived from Ae. tauschii was inherited as a recessive trait which was controlled by one gene, located on chromosome 2D.

Axonal regeneration and sprouting as a potential therapeutic target for nervous system disorders

Nervous system disorders are prevalent health issues that will only continue to increase in frequency as the population ages.Dying-back axonopathy is a hallmark of many neurologic diseases and leads to axonal disconnection from their targets,which in turn leads to functional impairment.During the course of many of neurologic diseases,axons can regenerate or sprout in an attempt to reconnect with the target and restore synapse function.In amyotrophic lateral sclerosis(ALS),distal motor axons retract from neuromuscular junctions early in the disease-course before significant motor neuron death.There is evidence of compensatory motor axon sprouting and reinnervation of neuromuscular junctions in ALS that is usually quickly overtaken by the disease course.Potential drugs that enhance compensatory sprouting and encourage reinnervation may slow symptom progression and retain muscle function for a longer period of time in ALS and in other diseases that exhibit dying-back axonopathy.There remain many outstanding questions as to the impact of distinct disease-causing mutations on axonal outgrowth and regeneration,especially in regards to motor neurons derived from patient induced pluripotent stem cells.Compartmentalized microfluidic chambers are powerful tools for studying the distal axons of human induced pluripotent stem cells-derived motor neurons,and have recently been used to demonstrate striking regeneration defects in human motor neurons harboring ALS disease-causing mutations.Modeling the human neuromuscular circuit with human induced pluripotent stem cells-derived motor neurons will be critical for developing drugs that enhance axonal regeneration,sprouting,and reinnervation of neuromuscular junctions.In this review we will discuss compensatory axonal sprouting as a potential therapeutic target for ALS,and the use of compartmentalized microfluidic devices to find drugs that enhance regeneration and axonal sprouting of motor axons.

Extrinsic inhibitors in axon sprouting and functional recovery after spinal cord injury

The limited axonal growth after central nervous system （CNS） injury such as spinal cord injury presents a major challenge in promoting repair and recovery. The literature in axonal repair has focused mostly on frank regeneration of injured axons. Here, we argue that sprouting of uninjured axons, an innate repair mech- anism of the CNS, might be more amenable to modulation in order to promote functional repair. Extrinsic inhibitors of axonal growth modulate axon sprouting after injury and may serve as the first group of therapeutic targets to promote functional repair.

Recent evidence for activity-dependent initiation of sympathetic sprouting and neuropathic pain

Traumatic injury or inflammatory irritation of the peripheral nervous system often leads to persistent pathophysiological pain states.It has been well-documented that,after peripheral nerve injury or inflammation,functional and anatomical alterations sweep over the entire peripheral nervous system including the peripheral nerve endings,the injured or inflamed afferent fibers,the dorsal root ganglion(DRG),and the central afferent terminals in the spinal cord.Among all the changes,ectopic discharge or spontaneous activity of primary sensory neurons is of great clinical interest,as such discharges doubtless contribute to the develop-ment of pathological pain states such as neuropathic pain.Two key sources of abnormal spontaneous activity have been identified following peripheral nerve injury:the injured afferent fibers(neuroma) leading to the DRG,and the DRG somata.The purpose of this review is to provide a global account of the abnormal spontaneous activity in various animal models of pain.Particular attention is focused on the consequence of peripheral nerve injury and localized inflammation.Further,mechanisms involved in the generation of spontaneous activity are also reviewed;evidence of spontaneous activity in contributing to abnormal sympathetic sprouting in the axotomized DRG and to the initiation of neuropathic pain based on new findings from our research group are discussed.An improved understanding of the causes of spontaneous activity and the origins of neuropathic pain should facilitate the development of novel strategies for effective treatment of pathological pain.

Changes in biochemical constituents and induction of early sprouting by triadimefon treatment in white yam(Dioscorea rotundata Poir.) tubers during storage

The ability of triadimefon(TDM),a triazolic fungicide,to alter the biochemical constituents and thereby minimizing the days required for sprouting in white yam(Dioscorea rotundata Poir.) tubers during storage under(30±2) °C in the dark,was studied.TDM at 20 mg/L was given to tubers by dipping the tubers in treatment solution containing 20 mg/L TDM on 10,25 and 40 d after storage(DAS).Starch,sugars,protein,amino acid contents as well as protease and α-amylase activities were estimated on 15,30 and 45 DAS from two physiological regions viz.,apical and basal regions of the tubers.In normal conditions(control) sprouting occurred on 70 to 80 DAS.The starch content decreased,while protein,amino acid,sugar contents and protease and α-amylase activities were increased due to TDM treatment and led to early sprouting.

Acrylamide inhibits nerve sprouting induced by botulinum toxin type A

Botulinum toxin type A is a potent muscle relaxant that blocks the transmission and release of acetylcholine at the neuromuscular junction. Intramuscular injection of botulinum toxin type A has served as an effective and safe therapy for strabismus and focal dystonia. However, muscular weakness is temporary and after 3-4 months, muscle strength usually recovers because function- al recovery is mediated by nerve sprouting and reconstruction of the neuromuscular junction. Acrylamide may produce neurotoxic substances that cause retrograde necrotizing neuropathy and inhibit nerve sprouting caused by botulinum toxin type A. This study investigated whether acrylamide inhibits nerve sprouting after intramuscular injection of botulinum toxin type A. A tibial nerve sprouting model was established through local injection of botulinum toxin type A into the right gastrocnemius muscle of Sprague-Dawley rats. Following intramuscular injection, rats were given intraperitoneal injection of 3% acrylamide every 3 days for 21 days. Nerve sprout- ing appeared 2 weeks after intramuscular injection of botulinum toxin type A and single-fiber electromyography revealed abnormal conduction at the neuromuscular junction I week after intra- muscular injection of botulinum toxin type A. Following intraperitoneal injection of acrylamide, the peak muscle fiber density decreased. Electromyography jitter value were restored to normal levels 6 weeks after injection. This indicates that the maximal decrease in fiber density and the time at which functional conduction of neuromuscular junction was restored were delayed. Addition- ally, the increase in tibial nerve fibers was reduced. Acrylamide inhibits nerve sprouting caused by botulinum toxin type A and may be used to prolong the clinical dosage of botulinum toxin type A.

Repairing the injured spinal cord: sprouting versus regeneration. Is this a realistic match?

The article by Meves and Zheng （2014） is addressing a continu- ous shift in the field of spinal cord injury （SCI） research that has occurred over the last century. Before that, the spinal cord was viewed as ＂hard wired＂ and treatment considerations were based on observations that axons in the periphery were able to regenerate, but those in the central nervous system （CNS） were not （David and Aguayo, 1981）.