Accounting for extinction dynamics unifies the geological and biological histories of Indo-Australian Archipelago.

Biogeographical reconstructions of the Indo-Australian Archipelago (IAA) have suggested a recent spread across the Sunda and Sahul shelves of lineages with diverse origins, which appears to be congruent with a geological history of recent tectonic uplift in the region. However, this scenario is challenged by new geological evidence suggesting that the Sunda shelf was never submerged prior to the Pliocene, casting doubt on the interpretation of recent uplift and the correspondence of evidence from biogeography and geology. A mismatch between geological and biogeographical data may occur if analyses ignore the dynamics of extinct lineages, because this may add uncertainty to the timing and origin of clades in biogeographical reconstructions. We revisit the historical biogeography of multiple IAA taxa and explicitly allow for the possibility of lineage extinction. In contrast to models assuming zero extinction, we find that all of these clades, including plants, invertebrates and vertebrates, have a common and widespread geographic origin, and each has spread and colonized the region much earlier than previously thought. The results for the eight clades re-examined in this article suggest that they diversified and spread during the early Eocene, which helps to unify the geological and biological histories of IAA.

Reflecting on Indonesia's young academy movement.

In the past three decades, there has been a rise in young academy movements in the Global North and South. Such movements, in at least Germany and the Netherlands, have been shown to be quite effective in connecting scientific work with society. Likewise, these movements share a common goal of developing interdisciplinary collaboration among young scientists, which contributes to the growth of a nation's-but also global-scientific endeavors. This paper focuses on the young academy movement in the fourth-largest country hosting the biggest Muslim population in the world, which is also the third-most populous democracy: Indonesia. We observe that there has been rising awareness among the young generation of scientists in Indonesia of the need to advocate for the use of sciences in responding to upcoming and current multidimensional crises. Science advocacy can be seen in their peer-based identification of Indonesia's future challenges, encompassing the fundamental areas for scientific inquiry, discovery, and intervention. We focus on the Indonesian Young Academy of Sciences (ALMI) and its network of young scientists. We describe ALMI's science communication practice, specifically SAINS45 and Science for Indonesia's Biodiversity, and how they have been useful for policymakers, media, and school engagements. The article closes with a reflection on future directions for the young academy movement in Indonesia and beyond.

The characteristics of stingless bee nests (Apidae: Meliponini) in the Cycloop Mountain Nature Reserve, Indonesia

Introduction: Stingless bees are widespread in tropical and subtropical regions. In Indonesia, the distribution of stingless bees are grouped in three regions, namely Indo-Malayan, Wallacea, and Indo-Australian. Ten species of stingless bees have been recorded in Papua, seven of which are endemic. The Cycloop Mountains Nature Reserve (CMNR) is one of the conservation area in Papua, Indonesia, for flora and fauna. Unfortunately, the study of the diversity of stingless bees in Papua has been limited. Objective: To measure the diversity, nesting sites, nest entrance characteristics and nest architecture of stingless bees. Methods: Observation of the stingless bee nests in the nature reserves and in the residential areas used a road sampling method and information from local people, respectively. A total of 22 colonies were studied. Results: Two species of stingless bee were found, namely Tetragonula sapiens (Cockerell, 1911) and Heterotrigona (Platytrigona) planifrons (Smith, 1865). The current study showed new distribution records for T. sapiens and H. planifrons in the CMNR. The nesting site of T. sapiens was commonly found in house foundation, while that of H. planifrons was in coconut palm cavities. The nest entrance of T. sapiens varied, i.e., elliptical, oval, rounded, irregular, horizontally or vertically elongated. Meanwhile, the nest entrance of H. planifrons was vertically elongated. The brood cells of T. sapiens varied, i.e., vertical, horizontal, or semi-clusters, while in H. planifrons was layered vertically. Conclusions: Two species of stingless bees found, T. sapiens and H. planifrons, showed a new distribution records and T. sapiens was a dominant species in Papua. The nest entrance of the species varied in shape, color, and texture.

Introducción: Las abejas sin aguijón están muy extendidas en las regiones tropicales y subtropicales. En Indonesia, la distribución de las abejas sin aguijón se agrupa en tres regiones: Indo-Malayan, Wallacea e Indo-Australian. Se han registrado diez especies de abejas sin aguijón en Papua, siete de las cuales son endémicas. La Reserva Natural de las Montañas Cycloop (CMNR) es una de las áreas para la conservación de flora y la fauna en Papua, Indonesia. Desafortunadamente, el estudio de la diversidad de abejas sin aguijón en Papua ha sido limitado. Objetivo: Medir la diversidad, los sitios de anidación y describir la arquitectura y características de entrada al nido de las abejas sin aguijón. Métodos: Se observaron los nidos de abejas sin aguijón en reservas naturales y áreas residenciales, mediante el método de muestreo de caminos e información de la población local, respectivamente. Se estudiaron 22 colonias. Resultados: Se encontraron dos especies de abejas sin aguijón, Tetragonula sapiens (Cockerell, 1911) y Heterotrigona (Platytrigona) planifrons (Smith, 1865). Este estudio mostró nuevos registros de distribución de T. sapiens y H. planifrons en el CMNR. El sitio de anidación de T. sapiens se encontró comúnmente en los cimientos de las casas, mientras que el de H. planifrons estaba en las cavidades de las palmas de coco. La forma de la entrada al nido de T. sapiens varió: elíptica, ovalada, redondeada, irregular, alargada horizontal o verticalmente. Mientras tanto, la entrada al de H. planifrons se alarga verticalmente. Las celdas de cría de T. sapiens variaron, entre verticales, horizontales o semi-racimos, mientras que en H. planifrons eran verticales. Conclusiones: Se encontraron dos especies de abejas sin aguijón, T. sapiens y H. planifrons, que mostraron nuevos registros de distribución y T. sapiens fue una especie dominante en Papúa. La entrada al nido de las especies varió en forma, color y textura.

Impact of Phylogenetic Tree Completeness and Mis-specification of Sampling Fractions on Trait Dependent Diversification Models.

Understanding the origins of diversity and the factors that drive some clades to be more diverse than others are important issues in evolutionary biology. Sophisticated SSE (state-dependent speciation and extinction) models provide insights into the association between diversification rates and the evolution of a trait. The empirical data used in SSE models and other methods is normally imperfect, yet little is known about how this can affect these models. Here, we evaluate the impact of common phylogenetic issues on inferences drawn from SSE models. Using simulated phylogenetic trees and trait information, we fitted SSE models to determine the effects of sampling fraction (phylogenetic tree completeness) and sampling fraction mis-specification on model selection and parameter estimation (speciation, extinction, and transition rates) under two sampling regimes (random and taxonomically biased). As expected, we found that both model selection and parameter estimate accuracies are reduced at lower sampling fractions (i.e., low tree completeness). Furthermore, when sampling of the tree is imbalanced across sub-clades and tree completeness is ≤ 60%, rates of false positives increase and parameter estimates are less accurate, compared to when sampling is random. Thus, when applying SSE methods to empirical datasets, there are increased risks of false inferences of trait dependent diversification when some sub-clades are heavily under-sampled. Mis-specifying the sampling fraction severely affected the accuracy of parameter estimates: parameter values were over-estimated when the sampling fraction was specified as lower than its true value, and under-estimated when the sampling fraction was specified as higher than its true value. Our results suggest that it is better to cautiously under-estimate sampling efforts, as false positives increased when the sampling fraction was over-estimated. We encourage SSE studies where the sampling fraction can be reasonably estimated and provide recommended best practices for SSE modeling. [Trait dependent diversification; SSE models; phylogenetic tree completeness; sampling fraction.].

Safeguarding Imperiled Biodiversity and Evolutionary Processes in the Wallacea Center of Endemism.

Wallacea-the meeting point between the Asian and Australian fauna-is one of the world's largest centers of endemism. Twenty-three million years of complex geological history have given rise to a living laboratory for the study of evolution and biodiversity, highly vulnerable to anthropogenic pressures. In the present article, we review the historic and contemporary processes shaping Wallacea's biodiversity and explore ways to conserve its unique ecosystems. Although remoteness has spared many Wallacean islands from the severe overexploitation that characterizes many tropical regions, industrial-scale expansion of agriculture, mining, aquaculture and fisheries is damaging terrestrial and aquatic ecosystems, denuding endemics from communities, and threatening a long-term legacy of impoverished human populations. An impending biodiversity catastrophe demands collaborative actions to improve community-based management, minimize environmental impacts, monitor threatened species, and reduce wildlife trade. Securing a positive future for Wallacea's imperiled ecosystems requires a fundamental shift away from managing marine and terrestrial realms independently.

Reconstruction of State-Dependent Diversification: Integrating Phenotypic Traits into Molecular Phylogenies.

The relative contribution of speciation and extinction into current diversity is certainly unknown, but mathematical frameworks that use genetic information have been developed to provide estimates of these processes. To that end, it is necessary to reconstruct molecular phylogenetic trees which summarize ancestor-descendant relationships as well as the timing of evolutionary events (i.e., rates). Nevertheless, diversification models show poor fit when assuming that single rate of speciation/extinction is constant over time and across lineages: species exhibit such a great variation in features that it is unlikely they give birth and die at the same pace. The state-dependent diversification framework (SSE) reconciles the species phenotypic variation with heterogeneous rates of diversification observed in a clade. This family of models allows testing contrasting hypotheses on mode of speciation, trait evolution, and its influence on speciation/extinction regimes. Although microbial species richness outnumbers diversity in plants and animals, diversification models are underused in microbiology. Here, we introduce microbiologists to models that estimate diversification rates and provide a detailed description of SSE models. Besides theoretical principles underlying the method, we also show how SSE analysis should be set up in R. We use pH evolution in Thaumarchaeota to explain its evolutionary dynamic in the light of SSE model. We hope this chapter spurs the study of trait evolution and evolutionary outcomes in microorganisms.

Conditioned medium of E17 rat brain cells induced differentiation of primary colony of mice blastocyst into neuron-like cells.

BACKGROUND: Conditioned medium is the medium obtained from certain cultured cells and contained secretome from the cells. The secretome, which can be in the form of growth factors, cytokines, exosomes, or other proteins secreted by the cells, can induce the differentiation of cells that still have pluripotent or multipotent properties. OBJECTIVES: This study examined the effects of conditioned medium derived from E17 rat brain cells on cells with pluripotent properties. METHODS: The conditioned medium used in this study originated from E17 rat brain cells. The CM was used to induce the differentiation of primary colonies of mice blastocysts. Primary colonies were stained with alkaline phosphatase to analyze the pluripotency. The morphological changes in the colonies were examined, and the colonies were stained with GFAP and Neu-N markers on days two and seven after adding the conditioned medium. RESULTS: The conditioned medium could differentiate the primary colony, beginning with the formation of embryoid-body-like structure; round GFAP positive cells were identified. Finally, neuron-like cells testing positive for Neu-N were observed on the seventh day after adding the conditioned medium. CONCLUSIONS: Conditioned medium from different species, in this case, E17 rat brain cells, induced and promoted the differentiation of the primary colony from mice blastocysts into neuron-like cells. The addition of CM mediated neurite growth in the differentiation process.

Effects of Eugenol on Memory Performance, Neurogenesis, and Dendritic Complexity of Neurons in Mice Analyzed by Behavioral Tests and Golgi Staining of Brain Tissue.

Eugenol, as the main component in clove, has neuroprotective abilities, including its effect to learning memory of mice. However, there is no evidence showing whether eugenol can expand the growth of dendrites in the brain. The objective of this research was to examine the effects of eugenol towards dendritic complexity of neurons, neurogenesis, and memory performance in hippocampus. A total of 21 mice were divided into three groups; (i) mice were administered 30 mg/kg bw eugenol orally, (ii) mice were administered 100 mg/kg bw eugenol orally, and (iii) mice were administered distilled water as control. Mice were kept for 30 consecutive days following the standard animal housing. The memory performance was observed through the Y-arm maze alternation, Novel Object Recognition (NOR), and Morris Water Maze (MWM) test. The brain was dissected and stained with FD Rapid Golgi StainingTM kit to observe dendrites in the dentate gyrus (DG) and cornu ammonis 1 (CA1) region; and Haematoxylin-Eosin (HE) staining to assess neurogenesis in the DG. Our results showed that eugenol enhanced putative neural stem cells (NPCs) and granular cells (GC) number, and also decrease neuronal cell death in DG (p<0.0001). Eugenol also increased dendritic complexity of neurons in DG region; while in CA1, eugenol has given a positive effect only on the basal area. Eugenol increased spatial and recognition memory in mice, indicated by a higher number of correct alternations and discrimination ratio compared to the control group (p<0.05), although escape latency in MWM did not show significant effect (p>0.05). As analyzed by behavioral tests and Golgi staining of brain tissue, eugenol can increase memory performance, neurogenesis, and dendritic complexity of neurons in the DG and CA1 basal region of brain in mice.

Effect of Conditioned Medium from IGF1-Induced Human Wharton's Jelly Mesenchymal Stem Cells (IGF1-hWJMSCs-CM) on Osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a chronic disease that attacks joints and bones which can be caused by trauma or other joint diseases. Stem cell and Conditioned Medium (CM) of stem cells are developed for OA therapy, which is minimally invasive. It can decrease inflammation and be a replacement for knee surgery. This study aimed to utilize human Wharton's Jelly-Mesenchymal Stem Cells (hWJMSCs) as an alternative OA therapy. METHODS: CM from hWJMSCs induced by IGF1 was collected. The OA cells model (IL1ß-CHON002) culture was treated as follows: 1) with hWJMSCs-CM 15% (v/v); 2) with hWJMSCs-CM 30% (v/v); 3) with IGF1-hWJMSCs (IGF1-hWJMSCs-CM) 15% (v/v); 4) with IGF1-hWJMSCs-CM 30% (v/v). Parameters including inflammatory cytokines (IL10 and TNFα), extracellular matrix degradation (MMP3 expression), and chondrogenic marker (COL2 expression) were determined. RESULTS: The most significant increase in COL2 chondrogenic markers was found in IL1ß-CHON002 treatment using 15% CM of hWJMSCs induced with IGF1. CM of hWJMSCs can reduce inflammatory cytokines (TNFα and IL10) and matrix degradation mediator MMP3. Better result was gained from IGF1-induced hWJMSCs-CM. CONCLUSION: CM of IGF1-hWJMSCs reduce inflammation while repairing injured joint in the human chondrocyte OA model.

Evolution of the bitter taste receptor TAS2R38 in colobines.

Bitter taste perception enables the detection of potentially toxic molecules and thus evokes avoidance behavior in vertebrates. It is mediated by bitter taste receptors, TAS2Rs. One of the best-studied TAS2R is TAS2R38. Phenylthiocarbamide (PTC) perception and TAS2R38 receptors vary across primate species, and this variation may be related to variation in dietary preferences. In particular, we previously found that the low sensitivity of TAS2R38s in Asian colobines likely evolved as an adaptation to their leaf-eating behavior. However, it remains unclear whether this low PTC sensitivity is a general characteristic of the subfamily Colobinae, a primate group that feeds predominantly on leaves. We performed genetic analyses, functional assays with mutant proteins, and behavioral analyses to evaluate the general characteristics of TAS2R38 in colobines. We found that PTC sensitivity is lower in TAS2R38s of African colobines than in TAS2R38s of omnivorous macaques. Furthermore, two amino acids shared between Asian and African colobines were responsible for low sensitivity to PTC, suggesting that the last common ancestor of extant colobines had this phenotype. We also detected amino acid differences between TAS2R38s in Asian and African colobines, indicating that they evolved independently after the separation of these groups.

Oral Administration of Incense Resin (Styrax benzoin) Extract Enhances Spatial Learning, Memory, and Dendrite Complexity of Mice

Abstract Hippocampus is a part of the brain that has a major role in spatial learning and memory which can be affected by herbal extracts. Incense resin (Styrax benzoin) has been used by local communities to improve intelligence. However, there is no scientific evidence of the functions of Styrax benzoin for regulating hippocampal function. The aim of this study was intended to analyze and investigate the effect of incense resin on learning, memory, and dendrite complexity of mice. Three months old male Deutch Democratic Yokohama (DDY) mice were injected orally with graded doses of 100, 150, and 200 mg/kg of incense resin aqueous extract daily for 30 days. Spatial learning and memory performance levels were tested with Y-maze alternation, novel object recognition, and Morris water maze. The branches and maximum dendritic span in the dentate gyrus were observed by the Golgi-Cox staining. Overall, our results showed that incense resin extract increased learning and memory ability, and the number of dendrite branching in the dentate gyrus.

Male Homosexual Preference: Femininity and the Older Brother Effect in Indonesia.

Male homosexual preference (MHP) is an evolutionary enigma because it is partially heritable and imposes a fertility cost. In occidental societies, homosexual men are feminized at various levels and they have more older brothers than heterosexual men. To evaluate whether femininity and the fraternal birth order (FBO) effect are universal features of MHP or not, we collected original data from homosexual men, heterosexual men, and heterosexual women from Java (Indonesia). Facial photographs were used to test whether homosexual faces are feminized when compared with heterosexual ones. We found that faces manipulated to resemble the average face of homosexual men are perceived as facially feminized, suggesting that homosexual men are facially feminized compared to heterosexual men, although a higher facial femininity was not captured by morphological analyses. Then, family data were used to detect differences in siblings' composition between homosexuals and heterosexuals. Homosexual men displayed a higher number of older brothers than heterosexual men, even when sibship size was controlled for, suggesting that the FBO effect exists in Indonesian populations. Independent of sexual orientation, men with older brothers seem more feminized than those without older brothers, consistent with the immune origin of the FBO effect. In conclusion, MHP in Indonesia is partially feminized and they have more older brothers. Such features are also associated with MHP in other cultural contexts, suggesting a cross-cultural effect of men homosexual preference. An evolutionary explanation is available for the feminizing effect, although the FBO effect remains unexplained even if proximal mechanisms start to be identified.

The Phosphofructokinase and Pyruvate Kinase Genes in Apis andreniformis and Apis cerana indica: Exon Intron Organisation and Evolution.

Genes related to carbohydrate metabolism have evolved rapidly in eusocial bees, including honey bees. However, the characterisation of carbohydrate metabolism genes has not been reported in Apis andreniformis or Apis cerana indica. This study aimed to characterise phosphofructokinase (PFK) and pyruvate kinase (PK) genes in these honey bee species and to analyse the evolution of the genus Apis using these genes. This study found the first data regarding A. andreniformis PFK and PK-like nucleotide sequences. A BLAST-n algorithm-based search showed that A. andreniformis and A. c. indica PFK and PK genes were homologous with those of Apis florea and Apis cerana cerana from Korea, respectively. Multiple alignments of PFKs from five Apis species showed many exon gains and losses, but only one among the PKs. Thus, the exon-intron organisation of the PK genes may be more conserved compare with that of the PFKs. Another evolutionary pattern indicated that more nucleotide substitutions occurred in Apis' PK than PFK genes. Deduced PFK amino acid sequences revealed a PFK consensus pattern of 19 amino acids, while the deduced PK amino acid sequences were predicted to have barrel and alpha/beta domains. Based on these two metabolism-related genes, The Neighbour-joining and Maximum likelihood phylogenetic trees are congruent and revealed that the A. andreniformis and A. florea group were in the basal position. Apis mellifera, A. cerana, and Apis dorsata formed a monophyletic clade, although the positions of A. mellifera and A. dorsata were different in the nucleotide- and amino acid-based phylogenetic trees.

Heterogeneity of Cells Population and Secretome Profile of Differentiated Cells from E17 Rat Neural Progenitor Cells.

Conditioned medium has now gained increasing interest since the development of secretome-based therapy. Various types of cells have been studied as a source of the secretome. One of them is neural progenitor cells (NPCs). These are cells that capable of differentiating into neurons as well as glial cells. Indeed, the study on NPCs has risen in the last few decades, but the study on the differentiated cells has not clearly described. The most common procedures that widely used to get the conditioned medium is starvation. However, cell starvation may cause environmental stress and become an apoptotic trigger for the cells. In this study, we analyzed the effect of starvation on differentiated cells from E17 rat neural progenitor cells (NPCs) based on cells characteristics and secretome profile. We found that starvation decreased cells viability and affected the heterogeneity of the cell population. Astrocytes survived more under nutrient deprivation conditions, and the progenitor cells showed a higher tendency to differentiate to glial cells than neurons. Duration of starvation also influenced the secretome profile, alterations found in protein types and also their function in the biological process. During 24 hours of starvation, cells secreted proteins that were used to maintain cell growth, stimulate differentiation, and produce energy, but there were also proteins that identified and involved in autophagy activation. After 48 hours of starvation, astrocytes that became the dominant cells secreted proteins that try to keep protecting the remaining neurons.

Neuronal Cell Death and Mouse (Mus musculus) Behaviour Induced by Bee Venom.

Neuronal cell death can occur in a tissue or organ, including the brain, which affects memory. The objectives of this study were to determine the dose of bee venom that causes neuronal death and analyse the alteration of mouse behaviour, focusing in particular on spatial memory. Fifteen male mice of Deutsche Denken Yoken (DDY) strain were divided into control and treatment groups. Bee venom was injected six times for two weeks intraperitoneally with 1.88 mg/kg, 3.76 mg/kg, 5.6 mg/kg, and 7.48 mg/kg doses of venom. Brain histology was studied using haematoxylin-eosin stained paraffin embedded 5 µm coronal sections. A Y maze test was used to assay behaviour. Parameters observed were the number of dead neurons and the percentage of mice with altered behaviour. ANOVA showed that the effects of bee venom were significantly different in the case of the neuronal death parameter but were not significantly different in the case of the mice behaviour parameter. Duncan's Multiple Range Test (DMRT) demonstrated that P4 (7.48 mg/kg) gave the highest effect of bee venom to promote neuronal death.

Intra-arterial Transplantation of Human Umbilical Cord Blood Mononuclear Cells in Sub-acute Ischemic Stroke Increases VEGF Expression in Rats.

Thrombolysis (rt-PA) is the only United States Food and Drug Administration (FDA) approved drug currently available. Unfortunately, its effect has been limited by the narrow therapeutic time window. Human cord blood mononuclear cells (cbMNC) is a promising treatment for ischemic stroke by forming collateral and neo-vascularization where it is one of the important factors that contribute to cell repair. Therefore, evaluation of neo-vascularization in sub-acute stroke may be beneficial for recovery. One group for healthy rat and three groups (n=6 per group) of male wistar rats have undergone permanent middle cerebral artery occlusion (MCAO). Transplantation 1x106 cells/kg of human cbMNC intra-arterially (IA) and intra-venously (IV) were administered after 7 days. Behavioural tests were performed before MCAO, 1 week after MCAO and at 3,9 and 14 days after cbMNC transplantation. Beta III tubulin protein (TUJ1), glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) antibody marker were evaluated. Spontaneous activity of transplanted rats by cbMNC have significantly improved compared to placebo group (p<0.05). Angiogenesis in IA group showed significant difference (P<0.001) when compared to IV and placebo respectively. The existence of neovascularization in the transplanted rats of cbMNC provide hope in accelerating repairment of the neuronal cells and functional outcome.

Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid.

Prenatal exposure to valproic acid (VPA), an established antiepileptic drug, has been reported to impair postnatal cognitive function in children born to VPA-treated epileptic mothers. However, how these defects arise and how they can be overcome remain unknown. Using mice, we found that comparable postnatal cognitive functional impairment is very likely correlated to the untimely enhancement of embryonic neurogenesis, which led to depletion of the neural precursor cell pool and consequently a decreased level of adult neurogenesis in the hippocampus. Moreover, hippocampal neurons in the offspring of VPA-treated mice showed abnormal morphology and activity. Surprisingly, these impairments could be ameliorated by voluntary running. Our study suggests that although prenatal exposure to antiepileptic drugs such as VPA may have detrimental effects that persist until adulthood, these effects may be offset by a simple physical activity such as running.

TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus.

Pathological conditions such as epilepsy cause misregulation of adult neural stem/progenitor populations in the adult hippocampus in mice, and the resulting abnormal neurogenesis leads to impairment in learning and memory. However, how animals cope with abnormal neurogenesis remains unknown. Here we show that microglia in the mouse hippocampus attenuate convulsive seizure-mediated aberrant neurogenesis through the activation of Toll-like receptor 9 (TLR9), an innate immune sensor known to recognize microbial DNA and trigger inflammatory responses. We found that microglia sense self-DNA from degenerating neurons following seizure, and secrete tumour necrosis factor-α, resulting in attenuation of aberrant neurogenesis. Furthermore, TLR9 deficiency exacerbated seizure-induced cognitive decline and recurrent seizure severity. Our findings thus suggest the existence of bidirectional communication between the innate immune and nervous systems for the maintenance of adult brain integrity.

Prenatal exposure to suberoylanilide hydroxamic acid perturbs corticogenesis.

Suberoylanilide hydroxamic acid (SAHA) is one of the epidrugs developed for cancer treatment that works epigenetically by inhibiting histone deacetylases (HDACs). SAHA has been reported to diffuse across the placenta and found in fetal plasma in preclinical study, implying that it can influence fetus if taken by pregnant cancer patients. However, report regarding this aspect and the study of in utero HDAC inhibition by SAHA especially on fate specification of neural stem/progenitor cells within the developing mammalian cortex, is yet unavailable. Here we show that transient exposure of SAHA to mouse embryos during prominent neurogenic period resulted in an enhancement of cortical neurogenesis, which is accompanied by an increased expression of proneuronal transcription factor Neurog1. Neurogenesis was enhanced due to the increase number of proliferating Tbr2+ intermediate progenitor cells following SAHA exposure. In this relation, we observed that SAHA perturbed neonatal cortical lamination because of the increased production of Cux1+ and Satb2+ upper-layer neurons, and decreased that of Ctip2+ deep-layer neurons. Furthermore, an upper-layer neuronal lineage determinant Satb2 was also up-regulated, whereas those of deep-layer ones Fezf2 and Ctip2 were down-regulated by SAHA treatment. Taken together, our study suggests that proper regulation of HDACs is important for precise embryonic corticogenesis.

Epigenetic regulation of neural stem cell fate during corticogenesis.

The cerebral cortex comprises over three quarters of the brain, and serves as structural basis for the sophisticated perceptual and cognitive functions. It develops from common multipotent neural stem cells (NSCs) that line the neural tube. Development of the NSCs encompasses sequential phases of progenitor expansion, neurogenesis, and gliogenesis along with the progression of developmental stages. Interestingly, NSCs steadfastly march through all of these phases and give rise to specific neural cell types in a temporally defined and highly predictable manner. Herein, we delineate the intrinsic and extrinsic factors that dictate the progression and tempo of NSC differentiation during cerebral cortex development, and how epigenetic modifications contribute to the dynamic properties of NSCs.