Developmental Neuroscience最新文献

{"title":"Comparative Single Cell Transcriptome Analysis of c-Met Receptor Expressing and Non-Expressing Projection Neurons in the Developing Frontal and Visual Cortices.","authors":"Ramin Ali Marandi Ghoddousi, Pat Levitt, Zia Rady, Kathie L Eagleson","doi":"10.1159/000548617","DOIUrl":"https://doi.org/10.1159/000548617","url":null,"abstract":"<p><strong>Introduction: </strong>Single cell transcriptomic analyses in adult mice show that cortical projection neuron (PN) subclasses exhibit heterogenous gene expression profiles that reflect their projection targets, and laminar and areal positions. Further analyses revealed that PNs within the same subclass also exhibit transcriptomic heterogeneity. Recent evidence suggests that differences in maturation state reflect one source of this heterogeneity. The MET receptor tyrosine kinase, a regulator of synapse maturation, is expressed in a subpopulation within cortical PN subclasses, providing an experimental model to address transcriptomic heterogeneity within developing PN subclasses.</p><p><strong>Methods: </strong>Single cell RNA sequencing and smFISH were used to identify transcriptomic differences between Met+ and Met- PN populations in the mouse visual and frontal cortices during the early phase of synapse formation and dendritic growth.</p><p><strong>Results: </strong>Analyses confirmed enrichment of Met in select PN subclasses and further identified astrocytes as the major source of its ligand, Hgf. No genes were expressed uniquely in Met+ or Met- PNs within a subclass; rather, there were graded differences in gene expression between the populations. While the identity of differentially expressed genes varied between subclass and cortical area, there was a consistent overrepresentation of genes associated with axon growth, as well as synapse structure, development and function, with a subset associated with the MET interactome. Further, compared to Met- PNs, expression differences in genes associated with maturation indicate less mature excitatory synapses and spines in the Met+ population at this age.</p><p><strong>Conclusion: </strong>The current findings provide support for the hypothesis that Met+ PNs are in a less mature state than Met- PNs within the same subclass. Further, the data are consistent with converging lines of biochemical and electrophysiological evidence that MET contributes to asynchronous maturation of developing cortical circuits.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-41"},"PeriodicalIF":2.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding Insights into KCTD7-Related Drug-Resistant Epilepsy: Three Novel Mutations in a Cohort of Iranian Pediatric Patients.","authors":"Sima Binaafar, Reza Shervin Badv, Ali Rashidi-Nezhad, Mehrdad Behmanesh","doi":"10.1159/000548627","DOIUrl":"https://doi.org/10.1159/000548627","url":null,"abstract":"<p><p>KCTD7-related epilepsy is a rare neurogenetic disorder characterized by marked genetic and phenotypic heterogeneity, typically presenting with early onset and often exhibiting poor response to conventional antiseizure medications. We performed exome sequencing in 134 Iranian pediatric patients with drug-resistant epilepsy and selected mutations in the KCTD7 gene. The pathogenicity of the identified variants was assessed using multiple in silico prediction tools and classified according to the ACMG guidelines. Additionally, we reviewed the genotype-phenotype correlations and treatment histories of all reported cases with KCTD7 mutations. Three novel homozygous variants-c.14C>T (p.Thr5Met), c.840delC (p.Ile281Serfs*11), and c.746T>G (p.Val249Gly)-were identified in four patients. Significant phenotypic heterogeneity was observed among patients, with disease severity ranging from mild to profound. Independent in silico analyses of each variant yielded concordant results, consistently predicting their potential to impact the structure and function of the KCTD7 protein. To date, 72 patients from 55 families have been reported, including 26.66% of homozygous cases born to non-consanguineous parents, and 37% of reported variants localized within BTB domain. Although 88.9% of patients experienced seizure onset before age two, clinical trajectories were highly variable. Among 45 patients with treatment data, valproate, levetiracetam, and clonazepam were the most frequently prescribed antiseizure medications; however, seizure control remained inconsistent. Notably, we observed subfertility in two heterozygous fathers, an unexpected finding that may suggest a potential role for KCTD7 beyond the central nervous system. These findings expand the mutational and phenotypic landscape of KCTD7-related epilepsy and underscore its clinical heterogeneity and therapeutic challenges.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-30"},"PeriodicalIF":2.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between cold-inducible RNA binding motif 3 and hypothermia effect in murine hypoxia-ischemia model measured by metabolic MRI.","authors":"Xiaodan Liu, Xiangning Jiang, Alkisti Mikrogeorgiou Capper, Nicholas Stewart, Will Byrne, Xiao Ji, Jacob Ellison, Duan Xu, Donna M Ferriero","doi":"10.1159/000548626","DOIUrl":"https://doi.org/10.1159/000548626","url":null,"abstract":"<p><strong>Introduction: </strong>The efficacy of therapeutic hypothermia (TH) for neonatal hypoxic-ischemic encephalopathy (HIE) is inconsistent, and the cause remains unclear. This study aimed to explore the role of cold stress protein in the TH-induced neuroprotection following hypoxia-ischemia (HI) using metabolic MRI.</p><p><strong>Methods: </strong>Postnatal day 10 (P10) mice underwent unilateral HI followed by treatments with therapeutic hypothermia (TH) or normothermia (NT). HI and sham mice were scanned at 4 h and 22 h following TH after injection of hyperpolarized 13C-1 labeled pyruvate. The dynamic HP-13C MRSIs were acquired to examine the cerebral metabolic profile, i.e., the conversion rate from pyruvate to lactate (kPL) and the ratio of lactate to pyruvate (Lac/Pyr) in the injured hemisphere. T2-weighted images (T2WI) and diffusion MR images (dMRIs) were acquired to identify the anatomical structures and assess the injury. Mice brains were collected during and at 0 h, 4 h, 12 h, 18 h and 22 h after treatments for western blot to investigate the time course of the levels of the cold stress protein (RNA binding motif 3, RBM3) and cell death markers (spectrin 145/150 and spectrin 120) changes. The cerebral metabolic profile, RBM3 and spectrin levels, and injury size were compared across groups and between specific timepoints. The relationship between the cerebral metabolic profile and RBM3 levels in HI+TH group was also evaluated.</p><p><strong>Results: </strong>We observed the upregulation of RBM3 during TH at 4 h and 22 h after TH. The spectrin 145/150 and spectrin 120 were unchanged over time in HI+TH group, whereas they significantly increased at 18 h and 22 h in HI+NT group. Additionally, the injury size was noticeably larger at 22 h in HI+NT group. Lower kPL and Lac/Pyr were observed at 4 h and 22 h after TH, with a negative correlation to RBM3 levels in HI+TH group.</p><p><strong>Conclusion: </strong>This study demonstrates that RBM3 may be one of the key factors associated with TH-induced neuroprotection by reducing the anaerobic glycolysis process in HI mice, suggesting RBM3 upregulation may enhance the efficacy of TH for neonatal HIE.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-22"},"PeriodicalIF":2.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Umbilical Cord Blood Serotonin Levels with Neurodevelopmental Outcomes.","authors":"Kally C O Apos Reilly Sparks, Lauren C Shuffrey, Rebecca N Siegel, Hannah Yueh, Morgan R Firestein, Amy J Elliott, Hein J Odendaal, George M Anderson, William P Fifer, Jeremy Veenstra-VanderWeele","doi":"10.1159/000547803","DOIUrl":"https://doi.org/10.1159/000547803","url":null,"abstract":"<p><strong>Introduction: </strong>Serotonin (5-hydroxytryptamine [5-HT]) plays an important role in early development, and fetal 5-HT has been reported to arise from placental and maternal sources. Previous human studies have established an association between maternal 5-HT levels and neurodevelopmental outcomes in populations with autism. In this study, we analyze umbilical cord blood and placental 5-HT levels at birth to further investigate the relationship of gestational 5-HT levels with birth outcomes and offspring cognitive development.</p><p><strong>Methods: </strong>Participants were enrolled in the Safe Passage Study conducted by the Prenatal Alcohol and SIDS and Stillbirth (PASS) Network. Infant cord blood and placental samples were collected postdelivery, and 5-HT levels were measured using high-performance liquid chromatography-fluorometric analysis. The Mullen Scales of Early Learning (MSEL) assessed child development at 12 months. Associations between 5-HT levels and birth outcomes or developmental outcomes were assessed using linear regression models.</p><p><strong>Results: </strong>No significant association was found between cord blood (n = 418) and placental (n = 89) 5-HT levels. Preterm birth was associated with lower cord blood 5-HT levels, and increasing gestational age among full-term infants was associated with higher cord blood 5-HT levels. Cord blood 5-HT was significantly associated with the Mullen Scales of Early Learning Composite Score, and follow-up analyses revealed a significant association between cord blood 5-HT and fine motor skills. No association was found between placental 5-HT and the Mullen composite score.</p><p><strong>Conclusion: </strong>To our knowledge, this study is the first to evaluate the relationship between placental 5-HT levels and cord blood 5-HT levels at birth. The lack of association suggests that cord blood 5-HT levels are likely to be a better index of fetal 5-HT exposure. Associations between cord blood 5-HT and child cognitive development are consistent with previous studies showing an association between maternal 5-HT levels and neurodevelopmental trajectories. Further research is needed to better characterize these relationships and to elucidate the distinct contributions of maternal, placental, and fetal 5-HT sources across developmental time points.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-12"},"PeriodicalIF":2.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human apolipoprotein E ε4 allele modulates energy substrate availability, seizure burden, mortality and hippocampal injury, cell death and inflammation after neonatal hypoxic-ischemic brain injury.","authors":"Michelle Nazareth, Sarah Ann Duck, Abigail Fassinger, Genesis Elmore, Charles Pinto, Michael Nugent, Mark St Pierre, Charles Lechner, Lauren L Jantzie, Frances J Northington, Susan J Vannucci, Lee J Martin, Raul Chavez-Valdez","doi":"10.1159/000548432","DOIUrl":"https://doi.org/10.1159/000548432","url":null,"abstract":"<p><strong>Introduction: </strong>Human apolipoprotein E allele ε4 (ApoE4) is the strongest genetic risk factor for some forms of adulthood neurodegeneration linked to energetic disturbances and inflammation. We hypothesized that ApoE4 also influences neonatal brain neurodegeneration after a hypoxic ischemic (HI) insult, resulting in energy substrates (i.e., glucose, ketone bodies) disturbances, hippocampal injury, cell death and inflammation.</p><p><strong>Methods: </strong>Right-sided brain HI was induced at P10 in wild type (wt, C57BL6) and humanized ApoE3 and ApoE4 mice with sham anesthesia-exposed littermates as controls. Seizure-like activity, survival, blood glucose (BG), and ketone bodies (KB) were determined immediately after the HI insult. The hippocampi were assessed 24h and 72h after the HI insult for residual volume, cell death (α-fodrin breakdown), inflammatory markers, and transcriptomics (RNAseq).</p><p><strong>Results: </strong>Wt, ApoE3 and ApoE4 mice were congenic (>99.8% transcriptome similarity). Female ApoE4 mice had worse seizures, lower survival and smaller residual hippocampal volumes than the ApoE3 mice. All three strains had lower BG after HI. ApoE4 mice also had lower KB. Low BG was associated with higher pro-inflammatory and cell death markers in the hippocampus in all HI genotype groups at 24h but more robustly in ApoE4 mice, and in combination with high KB, was strongly linked to cell death (greater α-fodrin breakdown).</p><p><strong>Conclusion: </strong>Humanized ApoE4, compared to ApoE3, causes greater hippocampal injury, cell death and inflammation after a neonatal HI insult in association with low BG and underutilized KB. The mechanisms behind these associations need further investigation.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-22"},"PeriodicalIF":2.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Reprogramming of Oligodendrocytes in Intrauterine Growth Restriction.","authors":"Hannah Peters, Camille M Fung, Robert W Dettman, Maria L V Dizon, Jill Chang","doi":"10.1159/000548455","DOIUrl":"10.1159/000548455","url":null,"abstract":"<p><p>Introduction Intrauterine growth restriction (IUGR) has been shown to adversely affect developing white matter, putting infants at risk for neurodevelopmental disability including cerebral palsy (CP). White matter injury (WMI) has been well documented in both human and animal studies of IUGR with sexual dimorphism. Currently the underlying cellular mechanisms leading to WMI in IUGR remain poorly understood but energy failure is a likely candidate. Methods To address these gaps, we evaluated for sex-specific changes to oligodendrocyte (OL) differentiation and the OL transcriptome leveraging cell-specific epitope tagging and RNA isolation in a placental insufficiency-induced IUGR mouse model. OL mitochondrial respiration was further evaluated using primary cell isolation and Agilent Seahorse technology. Results We found an early sex-specific arrest of OL differentiation in IUGR females, which was followed by late catch-up differentiation and proliferation. Cell-specific RNA sequencing demonstrated downregulation of genes involved in oxidative phosphorylation (OXPHOS) in IUGR. IUGR males demonstrated a greater downregulation of electron transport chain (ETC) genes and proteins than their IUGR female counterparts. Quantification of O4+ oligodendrocyte mitochondrial respiration also demonstrated decreased ATP generation in IUGR males via OXPHOS that was consistent with ETC gene and protein expression findings. Conclusion Our findings demonstrate sex-specific differences in OL differentiation and in mitochondrial metabolism in IUGR. These results provide insight into the different neurodevelopmental outcomes seen between IUGR males and females. These results also lay the foundation for investigation into targeted nutritional and pharmacologic management.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-22"},"PeriodicalIF":2.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Synaptopathy and Sex Differences in Recognition Memory from Neonatal Staphylococcus epidermidis Infection.","authors":"Wing Ki Chan, Seyedeh Marziyeh Jabbari Shiadeh, Janne Lenzig, Pernilla Svedin, Sofia Rasmusson, Oceane Vigne, Vanessa Veit, Tetyana Chumak, Maryam Ardalan, Carina Mallard","doi":"10.1159/000548381","DOIUrl":"https://doi.org/10.1159/000548381","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus epidermidis (SE) is a predominant hospital-acquired bacterium leading to late-onset sepsis in preterm infants. Recent findings have suggested that postnatal S. epidermidis infection is associated with short-term neurodevelopmental consequences. However, the potential effects of postnatal SE infection on long-term neuronal plasticity and cognitive functions, which are sensitive to early-life brain insults, remain unclear. In light of these findings, we investigated the effects of postnatal SE infection on recognition memory function using a neonatal mouse model.</p><p><strong>Methods: </strong>On postnatal day 4, male and female C57Bl/6 mice were injected intraperitoneally with either 3.5 × 107 colony-forming units of SE or sterile saline. On postnatal day 45 (± 5 days), the mice were subjected to the Novel Object Recognition Test (NORT) to assess recognition memory function. Following NORT, the brains of the mice were collected for neuronal plasticity analyses by considering maturation of neurons and 3-D analysis of synaptic plasticity and hippocampal, measuring the Nerve growth factor (NGF) expression.</p><p><strong>Results: </strong>Postnatal SE infection induced long-term, sex-specific effects on recognition memory and hippocampal neuroplasticity. Female SE-infected mice showed enhanced recognition memory, whereas males showed no significant difference in the recognition memory after neonatal SE infection. At the cellular level, both sexes displayed a significant decrease in doublecortin-positive (DCX⁺) neurons in the dentate gyrus after SE infection, indicating impaired neuroplasticity. However, male mice showed increased spine density, particularly of immature thin spines and disrupted spatial organization of spines, while females demonstrated no change in spines. Notably, SE infection elevated hippocampal NGF expression in males, but not in females, suggesting sex-specific molecular responses that may contribute to the observed differences in neuroplasticity and cognitive outcomes.</p><p><strong>Conclusion: </strong>This study demonstrates that postnatal SE infection induces long-lasting, sex-specific changes in recognition memory. Early-life immune activation disrupted hippocampal neuroplasticity, with males showing greater vulnerability. These findings indicate distinct neurodevelopmental trajectories shaped by neonatal immune challenges in preterm infants, with implications for understanding sex-specific cognitive outcomes.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-33"},"PeriodicalIF":2.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligodendrogenesis Inhibition in the Juvenile and Adolescent Periods Differentially Alters Myelin in Mice.","authors":"Lisa M Gazdzinski, Jordan Mak, Kosaran Gumarathas, Miranda Mellerup, Armand Collin, John G Sled, Brian J Nieman, Anne L Wheeler","doi":"10.1159/000547880","DOIUrl":"10.1159/000547880","url":null,"abstract":"<p><strong>Introduction: </strong>The timing of myelination during development varies spatially according to the evolving functional demands of the maturing brain and is likely a mechanism of plasticity that contributes to sensitive periods of brain development during which the brain has heightened susceptibility to environmental influences. Disruption to this myelination process is therefore likely to have spatially and temporally heterogeneous effects. Myelinating oligodendrocytes arise from the differentiation of oligodendrocyte precursor cells, a process that depends on the transcription factor Myrf. In this study, the inducible Myrf conditional knockout mouse model is leveraged to characterize the impact of inhibiting oligodendrogenesis during the juvenile or adolescent period on white matter tracts with different timing of maturation.</p><p><strong>Methods: </strong>Electron microscopy (EM) was used to quantify the fraction of myelinated axons, axon diameter, and myelin thickness, or T2- and diffusion-weighted MRI (dMRI) were used to compute white matter volumes and measures sensitive to microstructure.</p><p><strong>Results: </strong>Mice with inhibited oligodendrogenesis during the juvenile period had a lower fraction of myelinated axons in the corpus callosum, which was not the case when oligodendrogenesis was halted during adolescence. Halting oligodendrogenesis in either developmental period had no effect on myelinated fraction in the earlier-to-mature optic tracts. Halted oligodendrogenesis during the juvenile period was detected with MRI as decreased volume of late-myelinating structures (corpus callosum, anterior commissure, and fornix) relative to controls. No group differences were observed in dMRI measures. Additionally, thinner myelin on larger calibre axons in the optics tracts of adolescent mice with halted oligodendrogenesis was detected with EM, but no MRI measures were sensitive to this difference.</p><p><strong>Conclusion: </strong>This study demonstrates that the impact of disrupting developmental oligodendrogenesis on white matter differs depending on the timing of disruption relative to the developmental stage of the structure. The results also highlight that morphological measures from structural MRI have high sensitivity to disrupted developmental myelination of white matter tracts.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-11"},"PeriodicalIF":2.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal Characterisation of Key Cortical Developmental Markers in the Developing Ferret Brain.","authors":"Rylie-May Alexa Hickmott, Mikaela Barresi, Abdulhameed Bosakhar, Sebastian Quezada, Anita Quigley, David W Walker, Mary Tolcos","doi":"10.1159/000547661","DOIUrl":"10.1159/000547661","url":null,"abstract":"<p><strong>Introduction: </strong>The ferret is an important model for studying corticogenesis and cortical gyrification due to its small size, condensed cortical development timeline, and postnatal onset of gyrification. Its cortical progenitor and neuronal diversity closely resemble those of humans. However, detailed histological data across the rostrocaudal axis at critical embryonic and postnatal stages remain limited, particularly for recently identified progenitor subpopulations. This study aimed to comprehensively characterise the spatiotemporal expression of key progenitor and neuronal markers throughout the rostrocaudal axis of the developing ferret cortex at critical embryonic and postnatal ages. In doing so, the study sought to establish a foundational, descriptive atlas of neurodevelopmental marker expression across key time points and cortical regions and layers.</p><p><strong>Methods: </strong>Immunofluorescent labelling of key neural progenitor and neuronal markers was performed on coronal ferret brain sections at embryonic (E34, E38) and postnatal (P2, P5, P15, P25) ages. Markers included PAX6, SOX2, TBR2, HOPX, CPLX3, CTIP2, SATB2, TUJ1, and DCX. Semi-quantitative analyses described the spatiotemporal distribution of each marker within defined cortical compartments along the rostrocaudal axis.</p><p><strong>Results: </strong>Early radial glial markers PAX6 and SOX2 were abundant in the ventricular zone at embryonic stages, progressively declining postnatally as the subventricular zone (SVZ) expanded. Intermediate progenitor cells labelled by TBR2 showed high abundance in the SVZ prenatally, with a marked decrease after birth. HOPX identified outer radial glia populations exhibiting distinct temporal and spatial distributions, with increasing presence in the subplate (SP) and cortical plate during postnatal stages. CPLX3 expression emerged postnatally, delineating mature SP neurons with regionally patterned maturation. Deep- and superficial-layer neuronal markers CTIP2 and SATB2 displayed orderly laminar emergence, indicating progressive cortical layer formation. General neuronal markers TUJ1 and DCX highlighted the maturation and migration of post-mitotic neurons, with spatiotemporal gradients reflecting cortical differentiation across regions.</p><p><strong>Conclusion: </strong>This detailed profiling fills critical gaps in the ferret histological record and serves as a valuable resource for investigations into mammalian corticogenesis using the ferret model. Through the integration of semi-quantitative assessments and qualitative analysis, this dataset contributes to the ongoing development of a detailed atlas of ferret brain development. These findings are expected to enhance the utility of the ferret model in neurodevelopmental research, particularly in translational contexts involving human cortical malformations.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-21"},"PeriodicalIF":2.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Mechanisms Underlying the Development and Evolution of the Mammalian Cerebrum Using Gyrencephalic Ferrets.","authors":"Kengo Saito, Narufumi Kameya, Nguyen Chi Tai, Toshihide Hamabe-Horiike, Yohei Shinmyo, Hiroshi Kawasaki","doi":"10.1159/000546646","DOIUrl":"10.1159/000546646","url":null,"abstract":"<p><strong>Background: </strong>The mammalian cerebrum has changed substantially during evolution. Neurons and glial cells have increased, and the cerebrum has expanded and folded. Although these evolutionary changes are believed to be important for acquiring higher cognitive functions, the molecular mechanisms underlying the development and evolution of the mammalian cerebrum are not fully understood. This is partially due to the difficulty in analyzing these mechanisms using only mice.</p><p><strong>Summary: </strong>To overcome this limitation, we developed genetic manipulation techniques for the cerebrum of gyrencephalic carnivore ferrets. Gene knockout in the ferret cerebrum was achieved using the CRISPR/Cas9 system.</p><p><strong>Key messages: </strong>This review highlights recent research from our lab and others on the mechanisms underlying the development and evolution of cortical folds using ferrets.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-14"},"PeriodicalIF":2.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}