New aspects of a small GTPase RAB35 in brain development and function

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or intermediates.These processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS superfamily.Dysfunction of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative diseases.Therefore,it is important to understand the physiological and pathological roles of RAB proteins in brain function.RAB35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell migration.RAB35 is also involved in neurite outgrowth and turnover of synaptic vesicles.We generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and function.These mice exhibited defects in anxiety-related behaviors and spatial memory.Strikingly,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal lamination.In contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex development.Recent studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's disease.In this review,we provide an overview of the current understanding of subcellular functions of RAB35.We also provide insights into the physiological role of RAB35 in mammalian brain development and function,and discuss the involvement of RAB35 dysfunction in neurodegenerative diseases.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

Exploring the dynamics of creative tourism:A tourist-centric perspective to achieve economic sustainable development

Creative tourism is a dynamic and innovative approach to tourism,which points out the importance of people's active participation and their immersion in such experiences.In a vernacular context,it should attract people(local and tourists)attention to accomplish its main goals.Despite its rich cultural and natural assets,Kurdistan province faces several challenges that impact its tourism potential.To achieve that,the study uses quantitative approach to thoroughly analyze and evaluate the components of creative tourism in this province.The research focuses on tourists who visited the province's ten towns during the spring and summer of 2023.Data collection utilized a Likert-scale questionnaire ranging from"very good"to"very poor".The study employed a semistructured questionnaire developed through qualitative interviews alongside a researcher-made questionnaire validated by experts from the University of Kurdistan.The qualitative questionnaire achieved a high-reliability score of 93%using Cronbach's alpha coefficient.In-depth interviews and literary research were conducted to identify creative tourism components and indicators,informing the development of a quantitative questionnaire.Data analysis was performed using SPSS 20 and AMOS software to scrutinize the survey findings,providing insights into enhancing creative tourism strategies in Kurdistan province.The results reveal the varying significance of these dimensions,with the cultural dimension identified as the most crucial(factor loading:0.95),followed by the social(0.92),economic(0.88),and managerial/political dimensions(0.83).The study highlights the importance of cultural planning,community engagement,and infrastructural support in fostering creative tourism.Furthermore,it explores the impact of creative industries,such as music and arts rooted in Kurdish culture,on tourism development.Economic diversification and spatialphysical considerations are critical factors in enhancing Kurdistan's appeal as a creative tourism destination,emphasizing sustainable growth and cultural preservation.

Lessons learned from the past serving as a guide for the future---On a state harmonious development from Naipaurs novel A bend in the river

Naipaul＇s novel A bend in the river illustrates the social confusion and people＇s destitution and wasting time in African countries after their national independence. An important reason is the president＇s self-publicity, tyrannical hess and destructiveness. Whereas the author＇s subjective suspicion is visible in democratic development of African countries. Indeed, in a country development, it is quite necessary to depend on its citizen, observing public feelings; controlling a state with science; benefiting citizen; utilizing resources; constructing homestead, intending creation with a harmonious and stable way.

Recent developments and applications on high-performance cast magnesium rare-earth alloys

During the past decades,with the increasing demands in lightweight structural materials,Mg alloys with low density and high performance have been extensively investigated and partly applied in some industries.Especially when rare earth(RE)elements are added as major alloying elements to Mg alloys,the alloy strength and creep resistance are greatly improved,which have promoted several series of Mg-RE alloys.This paper reviews the progress and developments of high-performance Mg-RE alloys in recent years with emphasis on cast alloys.The main contents include the alloy design,melt purification,grain refinement,castability,novel liquid casting and semisolid forming approaches,and the industrial applications or trials made of Mg-RE alloys.The review will provide insights for future developments of new alloys,techniques and applications of Mg alloys.

Association between Pre-pregnancy Body Mass Index and Offspring Neuropsychological Development from 1 to 24 Months of Age: A Birth Cohort Study in China

Objective To explore the interactions between pre-pregnancy body mass index(BMI) and age on offspring neuropsychological development from 1 to 24 months in China.Methods In this birth cohort study, a total of 2,253 mother-child pairs were enrolled in Tianjin, China,between July 2015 and May 2018. The China Developmental Scale for Children was used to assess developmental quotient(DQ) of children aged from 1 to 24 months.Results Mixed-models analysis revealed significant age × pre-pregnancy BMI interactions for total DQ and five neurobehavioral domains(gross motor, fine motor, adaptive, language, and social;P < 0.001).Age × pre-pregnancy BMI ≥ 25 kg/m^2 was associated with a negative effect on total DQ and five neurobehavioral domains, as compared to pre-pregnancy BMI < 25 kg/m^2(P < 0.01). Multiple comparisons showed pre-pregnancy BMI ≥ 25 kg/m^2 of mothers had a positive effect on child total DQ at the age of 1 month but a negative effect at 24 months(P < 0.05).Conclusions This study supported the age × pre-pregnancy BMI interaction on offspring neuropsychological development. It also revealed a short-term positive impact of high pre-pregnancy BMI on neuropsychological development at 1 month of age, but a long-term negative effect(from 1 to24 months).

GAMYB transcription factor LoMYB65 from lily plays a vital role in pollen development

Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.Here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.

Effect of Reelin signaling on pre-plate splitting during cerebral cortex development

The development of the 6-layered cerebral neocortex is one of the most important events during nervous system development, and disturbances could result in various malformations, causing clinically intractable diseases, such as epilepsy and cerebral palsy. Pre-plate splitting is the first developmental step of the cortical plate formation. Without correct pre-plate splitting, normal cerebral cortex structures are disturbed. The Reelin-Dabl molecular pathway plays a critical role during cerebral cortex development, and deficiencies in this pathway result in failed pre-plate splitting and an inverted cortical plate. This paper summarizes findings involving Reelin and pre-plate splitting and further explores the precise role of Reelin during pre-plate splitting.

Parabrachial neuron development: Effects of pre- and neonatal undernutrition in the rat

Pre-and neonatal fasting in the rat has been used as an experimental model to obtain information on how the newborn gustatory system can be damaged, in- terfering with the basic sensory and hedonic proc- esses to different tastants. Fasting during the prenatal period and for 24 days postnatally results in signifi- cant reductions of body and brain weight, number of branches, dendritic density, and cross-sectional area of the PBN multipolar neurons in the central lateral and central medial subnucleus particularly at post- natal days 20 and 30. Furthermore, the underfeeding paradigm affected more the middle portions of the dendritic tree than other parts of the neurons possibly disturbing the afferent characteristics of neuronal acti- vity propagation that may partly disrupt the elabora- tion of synaptic plasticity at later ages. These findings may play a role in the development of complex physio- logical phenomena such as food intake, taste discrimi- nation, learning taste aversion, and appetitive beha- vior.

Re-Evaluating Media Richness Theory in Software Development Settings

Software development teams communicate differently by using a variety of communication tools. Successful communication leads to competitive software based on clear and quickly delivered re-quirements, as well as smoothness in bug reporting and explanation. Agile and Waterfall software development approaches have both addressed the importance of communication for their process. However, neither Agile nor Waterfall has guaranteed communication effectiveness during their development lifecycle. In this study we highlight the main differences between Agile and Waterfall approaches in the light of Media Richness Theory (MRT). We also identify the preferred commu-nication tools during a project’s lifecycle using both Agile and Waterfall models separately. A mixed-method approach was employed in this study incorporating quantitative and qualitative data from interviews and a multilingual web-based survey. The results are presented descriptively and statistically and a rank ordering of communication tools based on our participants’ preferences leads to a better understanding of how to select the best tool in a given situation. Thus a new updated MRT ranking model tailored for software development environment was developed, as well as, we conclude that communication tools are employed differently based on project stages and team member’s role. These differences in using communication tools could be also attributed to the type of transferable information or personal preferences.

Psychomotor Development of Low Birth Weight Infants at the “Mère-Enfant” University Hospital Centre (UHC) of Libreville

Introduction: Low birth weight is a key indicator of newborn health. The objective of this study was to contribute to the reduction of low birth weight-related morbidity and mortality. Patients and Methods: cohort study conducted from January 2019 to July 2020 at the “Mère-Enfant” University Hospital Centre (UHC) of Libreville. All newborns with a birth weight 2500 g were included. The clinical data of patients were studied. They were followed over a period of 12 months and assessed psychomotorly by the Brunet-Lézine scale. Results: 1260/9035 births of low birth weight (14.0%) were observed, and 300 among them were included. The mortality rate was 27.0% (81) and 219 were followed for 12 months. The sex ratio was 0.8, the average birth weight was 2008.6 ± 215.2 g. The average gestational age was 34 ± 12 weeks with 75.3% prematurity. An infant disease was observed in 61.6% of cases and respiratory pathologies were more observed except at 3 months of age where the proportion of digestive pathologies was 20.5%. At the time of the last consultation at 12 months of life, 76.2% of infants had no pathology. The quotients of postural development, language and coordination were normal (between 110 - 70) respectively in 75.4%, 99.1% and 68% of cases at the age of 12 months. The psychomotor development quotient was correlated with the birth weight in the language area r = 0.15 (p = 0.024), posture r = 0.15 (p = 0.015) and coordination r = 0.15 (p = 0.026) respectively. Conclusion: Low birth weight is a public health problem at UHCME-JEF. Despite the fact that psychomotor development can be said to be satisfactory, many efforts remain to be made to reduce low birth weight levels and improve survival.

Histochemical study of the pre- and postnatal development of acetylcholinesterase in the rat spinal cord

The distribution of acetylcholinesterase(AChE)-positive structures in the developing rat spinal cord was studied with AChE-histochemistry.AChE-positive perikarya were first seen on embryonic day 14(E14) in the ventrolateral portion of the spinal cord.From that time onward.AChE=containing cells appeared gradually in the intermediate gray,dorsal horn and lateral spinal nucleus of the spinal cord in a ventral-to-dorsal,and lateral-to-medial order.No obvious rostral-to-caudal sequence was found.At birth,the distribution pattern of AChE-positive perikarya was basically similar to that in adults.After birth a dramatic increase in the AChE staining intensity extended from postnatal day 5(P5) to postnatal day 21(P21),In addition,two phases of transient AChE staining were observed in the external surface of the dorsal horn from embryonic day 15(E15) to embryonic day 21(E21) and in the marginal layer from embryonic day 21(E21) to postnatal day 14(P14),respectively.

Nutrition impacts of non-solid cooking fuel adoption on under-five children in developing countries

This paper examines the nutrition impacts of using non-solid cooking fuel on under-five children in developing countries.We draw on data from more than 1.12 million children in 62 developing countries from the Demographic and Health Surveys(DHS).Results from both fixed effects(FE)and instrumental variable(IV)estimates show that using non-solid cooking fuel significantly improves the nutrition outcomes of under-five children.Compared with their peers from households mainly using solid fuel,children from households mainly using non-solid fuel exhibit a lower probability of experiencing stunting(by 5.9 percentage points)and being underweight(by 1.2 percentage points).Our further investigation provides evidence for several underlying mechanisms,such as improved indoor air quality,induced reduction in children’s respiratory symptoms,benefits on maternal health,and reduction in maternal time spent on fuel collection or cooking.Heterogenous analyses suggest that the nutrition benefits of using non-solid cooking fuel are more prominent among boys,children above three years old,and those from households of lower socioeconomic status,rural areas,and Southeast Asia.

A dynamic regulation of nitrogen on floret primordia development in wheat

Nitrogen(N)fertilization is critical for spike and floret development,which affects the number of fertile florets per spike(NFFs).However,the physiological regulation of the floret development process by N fertilization is largely unknown.A high temporal-resolution investigation of floret primordia number and morphology,dry matter,and N availability was conducted under three N fertilization levels:0(N0),120(N1)and 240(N2)kg ha^(−1).Interestingly,fertile florets at anthesis stage were determined by those floret primordia with meiotic ability at booting stage:meiotic ability was a threshold that predicted whether a floret primordium became fertile or abortive florets.Because the developmental rate of the 4th floret primordium in the central spikelet was accelerated and then they acquired meiotic ability,the NFFs increased gradually as N application increased,but the increase range decreased under N2.There were no differences in spike N concentration among treatments,but leaf N concentration was increased in the N1 and N2 treatments.Correspondingly,dry matter accumulation and N content of the leaf and spike in the N1 and N2 treatments was increased as compared to N0.Clearly,optimal N fertilization increased leaf N availability and transport of assimilates to spikes,and allowed more floret primordia to acquire meiotic ability and become fertile florets,finally increasing NFFs.There was no difference in leaf N concentration between N1 and N2 treatment,whereas soil N concentration at 0–60 cm soil layers was higher in N2 than in N1 treatment,implying that there was still some N fertilization that remained unused.Therefore,improving the leaf’s ability to further use N fertilizer is vital for greater NFFs.

Research on Developing an Assessment Scale for Tourism Experience Elements of Ancient Shu Road Heritage Trail

Cultural ancient roads,known in Chinese as gudao,serve as heritage trails that carry historical exchanges across various regions in China.Due to their extensive preservation,wide geographical distribution,diverse thematic variations,and considerable tourist appeal,these paths have emerged as representative heritage trails,increasingly transforming into a novel tourism product experience that is highly favored by tourists and recognized by government authorities.However,research on ancient roads for tourism in China currently lacks a systematic theoretical framework,as well as relevant policies,regulations,and standards to guide their practical development.Therefore,there is a pressing need to draw upon international best practices and conduct foundational research to develop an experience element system that aligns with the perceptions,behaviors,and consumption characteristics of Chinese tourists,thereby advancing theoretical exploration in this field.This study focuses on the representative Ancient Shu Road as a case study and employs a mixed-method approach that integrates qualitative and quantitative research.It aims to construct a tourist-centric scale for the experience elements of ancient road tourism while analyzing the interactive relationship between these experience elements and tourist needs.This study addresses a significant gap in the development of indicator systems for domestic studies of ancient road tourism experiences.Ultimately,the study establishes a comprehensive scale that encompasses three core categories—trail resources and environment,facilities and services,and modes of tourism activities—along with eight primary dimensions:core resources,surrounding cultural environment,surrounding natural environment,tourism reception facilities and services,infrastructure and support services,information facilities and information services,and outdoor and recreational activities.This scale consists of thirty-two specific items,providing a robust reference for future research endeavors.Additionally,the study proposes specific development strategies related to key mechanisms,spatial configuration,and facility construction to enhance the overall development of ancient road tourism.

Conventional Geothermal Systems and Unconventional Geothermal Developments: An Overview

This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal systems have the heat, permeability and fluid, requiring only drilling down to °C, normal heat flow or decaying radiogenic granite as heat sources, and used in district heating. Medium-temperature (MT) 100°C - 190°C, and high-temperature (HT) 190°C - 374°C resources are mostly at plate boundaries, with volcanic intrusive heat source, used mostly for electricity generation. Single well capacities are °C - 500°C) and a range of depths (1 m to 20 Km), but lack permeability or fluid, thus requiring stimulations for heat extraction by conduction. HVAC is 1 - 2 m deep and shallow geothermal down to 500 m in wells, both capturing °C, with °C are either advanced by geothermal developers at <7 Km depth (Enhanced Geothermal Systems (EGS), drilling below brittle-ductile transition zones and under geothermal fields), or by the Oil & Gas industry (Advanced Geothermal Systems, heat recovery from hydrocarbon wells or reservoirs, Superhot Rock Geothermal, and millimeter-wave drilling down to 20 Km). Their primary aim is electricity generation, relying on closed-loops, but EGS uses fractures for heat exchange with earthquake risks during fracking. Unconventional approaches could be everywhere, with shallow geothermal already functional. The deeper and hotter unconventional alternatives are still experimental, overcoming costs and technological challenges to become fully commercial. Meanwhile, the conventional geothermal resources remain the most proven opportunities for investments and development.

Development and technology status of energy storage in depleted gas reservoirs

Utilizing energy storage in depleted oil and gas reservoirs can improve productivity while reducing power costs and is one of the best ways to achieve synergistic development of"Carbon Peak–Carbon Neutral"and"Underground Resource Utiliza-tion".Starting from the development of Compressed Air Energy Storage(CAES)technology,the site selection of CAES in depleted gas and oil reservoirs,the evolution mechanism of reservoir dynamic sealing,and the high-flow CAES and injection technology are summarized.It focuses on analyzing the characteristics,key equipment,reservoir construction,application scenarios and cost analysis of CAES projects,and sorting out the technical key points and existing difficulties.The devel-opment trend of CAES technology is proposed,and the future development path is scrutinized to provide reference for the research of CAES projects in depleted oil and gas reservoirs.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.