Astrogenesis in the murine dentate gyrus is a life-long and dynamic process.

Astrocytes are highly abundant in the mammalian brain, and their functions are of vital importance for all aspects of development, adaption, and aging of the central nervous system (CNS). Mounting evidence indicates the important contributions of astrocytes to a wide range of neuropathies. Still, our understanding of astrocyte development significantly lags behind that of other CNS cells. We here combine immunohistochemical approaches with genetic fate-mapping, behavioural paradigms, single-cell transcriptomics, and in vivo two-photon imaging, to comprehensively assess the generation and the proliferation of astrocytes in the dentate gyrus (DG) across the life span of a mouse. Astrogenesis in the DG is initiated by radial glia-like neural stem cells giving rise to locally dividing astrocytes that enlarge the astrocyte compartment in an outside-in-pattern. Also in the adult DG, the vast majority of astrogenesis is mediated through the proliferation of local astrocytes. Interestingly, locally dividing astrocytes were able to adapt their proliferation to environmental and behavioral stimuli revealing an unexpected plasticity. Our study establishes astrocytes as enduring plastic elements in DG circuits, implicating a vital contribution of astrocyte dynamics to hippocampal plasticity.

Virological assessment of hospitalized patients with COVID-2019.

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.

Dissecting the spatiotemporal diversity of adult neural stem cells.

Adult stem cells are important for tissue turnover and regeneration. However, in most adult systems it remains elusive how stem cells assume different functional states and support spatially patterned tissue architecture. Here, we dissected the diversity of neural stem cells in the adult zebrafish brain, an organ that is characterized by pronounced zonation and high regenerative capacity. We combined single-cell transcriptomics of dissected brain regions with massively parallel lineage tracing and in vivo RNA metabolic labeling to analyze the regulation of neural stem cells in space and time. We detected a large diversity of neural stem cells, with some subtypes being restricted to a single brain region, while others were found globally across the brain. Global stem cell states are linked to neurogenic differentiation, with different states being involved in proliferative and non-proliferative differentiation. Our work reveals principles of adult stem cell organization and establishes a resource for the functional manipulation of neural stem cell subtypes.

MR imaging after patellar MACI and MPFL reconstruction: a comparison of isolated versus combined procedures.

OBJECTIVE: To qualitatively and quantitatively evaluate the 2.5-year MRI outcome after Matrix-associated autologous chondrocyte implantation (MACI) at the patella, reconstruction of the medial patellofemoral ligament (MPFL), and combined procedures. METHODS: In 66 consecutive patients (age 22.8 ± 6.4years) with MACI at the patella (n = 16), MPFL reconstruction (MPFL; n = 31), or combined procedures (n = 19) 3T MRI was performed 2.5 years after surgery. For morphological MRI evaluation WORMS and MOCART scores were obtained. In addition quantitative cartilage T2 and T1rho relaxation times were acquired. Several clinical scores were obtained. Statistical analyses included descriptive statistics, Mann-Whitney-U-tests and Pearson correlations. RESULTS: WORMS scores at follow-up (FU) were significantly worse after combined procedures (8.7 ± 4.9) than after isolated MACI (4.3 ± 3.6, P = 0.005) and after isolated MPFL reconstruction (5.3 ± 5.7, P = 0.004). Bone marrow edema at the patella in the combined group was the only (non-significantly) worsening WORMS parameter from pre- to postoperatively. MOCART scores were significantly worse in the combined group than in the isolated MACI group (57 ± 3 vs 88 ± 9, P < 0.001). Perfect defect filling was achieved in 26% and 69% of cases in the combined and MACI group, respectively (P = 0.031). Global and patellar T2 values were higher in the combined group (Global T2: 34.0 ± 2.8ms) and MACI group (35.5 ± 3.1ms) as compared to the MPFL group (31.1 ± 3.2ms, P < 0.05). T2 values correlated significantly with clinical scores (P < 0.005). Clinical Cincinnati scores were significantly worse in the combined group (P < 0.05). CONCLUSION: After combined surgery with patellar MACI and MPFL reconstruction inferior MRI outcomes were observed than after isolated procedures. Therefore, patients with need for combined surgery may be at particular risk for osteoarthritis.

Evaluating User Perceptions of a Vibrotactile Feedback System in Trunk Stabilization Exercises: A Feasibility Study.

Low back pain patients often have deficits in trunk stability. For this reason, many patients receive physiotherapy treatment, which represents an enormous socio-economic burden. Training at home could reduce these costs. The problem here is the lack of correction of the exercise execution. Therefore, this feasibility study investigates the applicability of a vibrotactile-controlled feedback system for trunk stabilisation exercises. A sample of 13 healthy adults performed three trunk stabilisation exercises. Exercise performance was corrected by physiotherapists using vibrotactile feedback. The NASA TLX questionnaire was used to assess the practicability of the vibrotactile feedback. The NASA TLX questionnaire shows a very low global workload 40.2 [29.3; 46.5]. The quality of feedback perception was perceived as good by the subjects, varying between 69.2% (anterior hip) and 92.3% (lower back). 80.8% rated the feedback as helpful for their training. On the expert side, the results show a high rating of movement quality. The positive evaluations of the physiotherapists and the participants on using the vibrotactile feedback system indicate that such a system can reduce the trainees fear of independent training and support the users in their training. This could increase training adherence and long-term success.

Impacts of cultivar and management practices on the diversity and population dynamics of mites in soybean crops.

The objective of this study was to evaluate the diversity and population dynamics of mites in soybean crops with different cultivars and management practices. The study was conducted in two soybean production fields in the municipalities of Mato Queimado (L1) and Três de Maio (L2), Rio Grande do Sul state, Brazil. Two transgenic cultivars were used, and insecticide applications varied among treatments. Sampling began at the V2 stage, with 60 leaves/area/collection that were sorted, mites were collected and identified using dichotomous keys. A total of 18,100 mites belonging to 12 species were found. Among the species, Tetranychus urticae Koch, Mononychellus planki (McGregor), and Tetranychus ludeni Zacher (Tetranychidae) were the most abundant, whereas the most abundant predatory mites were the phytoseiids Neoseiulus californicus McGregor and Neoseiulus idaeus Denmark and Muma, with N. idaeus being more abundant and present in all areas. The acarofauna was influenced by environmental conditions and management practices. Neoseiulus idaeus was commonly associated with populations of M. planki, T. ludeni, and T. urticae. Neoseiulus californicus tolerated pesticide use but was affected by severe water stress, whereas N. idaeus tolerated periods of low relative humidity and high temperatures.

Does pre-incubation in selective-enrichment media improve the detection of diarrheagenic Escherichia coli using the RIDA®GENE PCR?

We aimed to investigate whether a selective pre-PCR enrichment step improves test performance of RIDA®GENE EHEC/EPEC to detect diarrheagenic Escherichia coli from stool samples. Each of the 250 stool samples was analyzed for the presence of stx1/2 and eae both with and without pre-PCR enrichment in selective broth. In comparison to a reference method, sensitivities for stx1/2 and eae with and without pre-PCR enrichment were 84% (95%CI 70-93) and 89% (stx1/2, 95%CI 76-96), and 71% (95%CI 58-81) and 72% (eae, 95%CI 60-82), respectively. Specificity exceeded 97% for both methods and target genes. In summary, pre-PCR broth enrichment did not improve test performance.

Repurposing of the antibiotic nitroxoline for the treatment of mpox.

The antiviral drugs tecovirimat, brincidofovir, and cidofovir are considered for mpox (monkeypox) treatment despite a lack of clinical evidence. Moreover, their use is affected by toxic side-effects (brincidofovir, cidofovir), limited availability (tecovirimat), and potentially by resistance formation. Hence, additional, readily available drugs are needed. Here, therapeutic concentrations of nitroxoline, a hydroxyquinoline antibiotic with a favourable safety profile in humans, inhibited the replication of 12 mpox virus isolates from the current outbreak in primary cultures of human keratinocytes and fibroblasts and a skin explant model by interference with host cell signalling. Tecovirimat, but not nitroxoline, treatment resulted in rapid resistance development. Nitroxoline remained effective against the tecovirimat-resistant strain and increased the anti-mpox virus activity of tecovirimat and brincidofovir. Moreover, nitroxoline inhibited bacterial and viral pathogens that are often co-transmitted with mpox. In conclusion, nitroxoline is a repurposing candidate for the treatment of mpox due to both antiviral and antimicrobial activity.

Lung Ultrasound as a Promising Diagnostic Tool for Primary Graft Dysfunction after Lung Transplantation.

PURPOSE: The aim of the study was to evaluate whether the quantification of B-lines via lung ultrasound after lung transplantation is feasible and correlates with the diagnosis of primary graft dysfunction. METHODS: Following lung transplantation, patients underwent daily lung ultrasound on postoperative days 1-3. B-lines were quantified by an ultrasound score based on the number of single and confluent B-lines per intercostal space, using a four-region protocol. The ultrasound score was correlated with the diagnosis of primary graft dysfunction. Furthermore, correlation analyses and receiver operating characteristics analyses taking into account ultrasound score, chest radiographs, and PaO2/FiO2 ratio were performed. RESULTS: A total of 32 patients (91 ultrasound measurements) were included, whereby 10 were diagnosed with primary graft dysfunction. The median B-line score was 5 [IQR: 4, 8]. There was a significant correlation between B-line score and the diagnosis of primary graft dysfunction (r = 0.59, p < 0.001). A significant correlation could also be seen between chest X-rays and primary graft dysfunction (r = 0.34, p = 0.008), but the B-line score showed superiority over chest X-rays with respect to diagnosing primary graft dysfunction in the receiver operating characteristics curves with an area under the curve value of 0.921 versus 0.708. There was a significant negative correlation between B-line score and PaO2/FiO2 ratio (r = -0.41, p < 0.001), but not between chest X-rays and PaO2/FiO2 ratio (r = -0.14, p = 0.279). CONCLUSION: The appearance of B-lines correlated well with primary graft dysfunction and outperformed chest radiographs.

Four-and-a-Half LIM-Domain Protein 2 (FHL2) Induces Neuropeptide Y (NPY) in Macrophages in Visceral Adipose Tissue and Promotes Diet-Induced Obesity.

Obesity is characterized by the expansion of the adipose tissue, usually accompanied by inflammation, with a prominent role of macrophages infiltrating the visceral adipose tissue (VAT). This chronic inflammation is a major driver of obesity-associated comorbidities. Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of various biological functions and the maintenance of the homeostasis of different tissues. In this study, we aimed to gain new insights into the expression and functional role of FHL2 in VAT in diet-induced obesity. We found enhanced FHL2 expression in the VAT of mice with Western-type diet (WTD)-induced obesity and obese humans and identified macrophages as the cellular source of enhanced FHL2 expression in VAT. In mice with FHL2 deficiency (FHL2KO), WTD feeding resulted in reduced body weight gain paralleled by enhanced energy expenditure and uncoupling protein 1 (UCP1) expression, indicative of activated thermogenesis. In human VAT, FHL2 was inversely correlated with UCP1 expression. Furthermore, macrophage infiltration and the expression of the chemokine MCP-1, a known promotor of macrophage accumulation, was significantly reduced in WTD-fed FHL2KO mice compared with wild-type (wt) littermates. While FHL2 depletion did not affect the differentiation or lipid metabolism of adipocytes in vitro, FHL2 depletion in macrophages resulted in reduced expressions of MCP-1 and the neuropeptide Y (NPY). Furthermore, WTD-fed FHL2KO mice showed reduced NPY expression in VAT compared with wt littermates, and NPY expression was enhanced in VAT resident macrophages of obese individuals. Stimulation with recombinant NPY induced not only UCP1 expression and lipid accumulation but also MCP-1 expression in adipocytes. Collectively, these findings indicate that FHL2 is a positive regulator of NPY and MCP-1 expression in macrophages and herewith closely linked to the mechanism of obesity-associated lipid accumulation and inflammation in VAT. Thus, FHL2 appears as a potential novel target to interfere with the macrophage-adipocyte crosstalk in VAT for treating obesity and related metabolic disorders.

Genetic characterization of varicella-zoster and HIV-1 viruses from the cerebrospinal fluid of a co-infected encephalitic patient, Ghana.

BACKGROUND: Encephalitis is a serious disease of the brain characterized by prodromal and specific neurological symptoms. HIV infections offer opportunistic viruses, such as Varicella-zoster virus (VZV), the chance to cause encephalitis in patients. There is a lack of information on the genetic diversity of VZV in Ghana and other parts of Africa which requires sequencing and characterization studies to address. The active evolution of HIV-1 in West Africa also requires continuous surveillance for the emergence of new genetic forms. CASE PRESENTATION: VZV was detected in the CSF sample of an 11-year-old patient presenting with symptoms of encephalitis by real-time PCR diagnostics. To identify possible unknown aetiological pathogens, next-generation sequencing was performed, and revealed an HIV-1 co-infection. Alignments of concatenated HIV-1 genome fragments in the gag, pol, vif, env and nef regions and a near-complete VZV genome were analyzed by Bayesian inference, and phylogenetic trees were generated. The VZV sequence belongs to clade 5 and the HIV-1 sequence is a member of the CRF02_AG predominant circulating recombinant form in Ghana. CONCLUSIONS: Diagnostic tests for CSF HIV would be useful where possible in patients presenting with encephalitis due to VZV and other opportunistic viruses in Kumasi to shed light on the role of HIV in encephalitis cases in Ghana. This report reaffirms the role of the CRF02_AG circulating recombinant form in HIV infections in Ghana and also gives a preliminary genetic characterization of VZV in Kumasi, Ghana.

Patellar instability MRI measurements are associated with knee joint degeneration after reconstruction of the medial patellofemoral ligament.

OBJECTIVE: To qualitatively and quantitatively evaluate the 2-year magnetic resonance imaging (MRI) outcome after MPFL reconstruction at the knee and to assess MRI-based risk factors that predispose for inferior clinical and imaging outcomes. MATERIALS AND METHODS: A total of 31 patients with MPFL reconstruction were included (22 ± 6 years, 10 female). MRI was performed preoperatively in 21/31 patients. Two-year follow-up MRI included quantitative cartilage T2 and T1rho relaxation time measurements at the ipsilateral and contralateral knee. T2relative was calculated as T2patellofemoral/T2femorotibial. Morphological evaluation was conducted via WORMS scores. Patellar instability parameters and clinical scores were obtained. Statistical analyses included descriptive statistics, t-tests, multivariate regression models, and correlation analyses. RESULTS: Two years after MPFL reconstruction, all patellae were clinically stable. Mean total WORMS scores improved significantly from baseline to follow-up (mean difference ± SEM, - 4.0 ± 1.3; P = 0.005). As compared to patients with no worsening of WORMS subscores over time (n = 5), patients with worsening of any WORMS subscore (n = 16) had lower trochlear depth, lower facetal ratio, higher tibial-tuberosity to trochlear groove (TTTG) distance, and higher postoperative lateral patellar tilt (P < 0.05). T2relative was higher at the ipsilateral knee (P = 0.010). T2relative was associated with preoperatively higher patellar tilt (P = 0.021) and higher TTTG distance (P = 0.034). TTTG distance, global T2 values, and WORMS progression correlated with clinical outcomes (P < 0.05). CONCLUSION: MPFL reconstruction is an optimal treatment strategy to restore patellar stability. Still, progressive knee joint degeneration and patellofemoral cartilage matrix degeneration may be observed, with patellar instability MRI parameters representing particular risk factors.

Hypoperfusion Intensity Ratio is Associated with Stroke Mechanism in Patients Undergoing Mechanical Thrombectomy.

BACKGROUND: Hypoperfusion Intensity Ratio (HIR), defined as Tmax >10s/Tmax >6s on computed tomography perfusion (CTP), and stroke mechanisms have been independently correlated with angiographic collaterals and patient outcomes. Slowly developing atherosclerotic stenosis may foster collateral development, whereas cardioembolic occlusion may occur before collaterals mature. We hypothesized that favorable HIR is associated with large artery atherosclerosis (LAA) stroke mechanism and good clinical outcome. METHODS: Retrospective study of consecutive endovascularly-treated stroke patients with intracranial ICA or MCA M1/M2 occlusions, who underwent CTP before intervention, between January 2018 and August 2021. Patients were dichotomized into LAA+ or LAA- based on presence of LAA on angiography. HIR was dichotomized into favorable (HIR+) or unfavorable (HIR-) groups based on published thresholds. Good early outcome was defined as discharge mRS of 0-2. Bivariate and multivariable logistic regression were performed. RESULTS: 143 patients met inclusion. 21/143 were LAA+ (15%) and 65/143 (45%) were HIR+. HIR+ was significantly more frequent in LAA+ patients (67% vs. 42%, p= 0.035). Controlling for demographics, stroke severity, imaging findings, and medical comorbidities, LAA+ remained independently associated with HIR+ (OR 5.37 [95% CI 1.43 - 20.14]; p=0.013) as did smaller infarction core volume (<30 mL of CBF <30%: OR 7.92 [95% CI 2.27 - 27.64]; p = 0.001). HIR+ was not associated with good clinical outcome. CONCLUSIONS: Large artery atherosclerosis was independently associated with favorable HIR in patients undergoing mechanical thrombectomy. While favorable HIR was associated with smaller pre-treatment core infarcts, reflecting more robust collaterals, it was not associated with good clinical outcome.

Large potential for crop production adaptation depends on available future varieties.

Climate change affects global agricultural production and threatens food security. Faster phenological development of crops due to climate warming is one of the main drivers for potential future yield reductions. To counter the effect of faster maturity, adapted varieties would require more heat units to regain the previous growing period length. In this study, we investigate the effects of variety adaptation on global caloric production under four different future climate change scenarios for maize, rice, soybean, and wheat. Thereby, we empirically identify areas that could require new varieties and areas where variety adaptation could be achieved by shifting existing varieties into new regions. The study uses an ensemble of seven global gridded crop models and five CMIP6 climate models. We found that 39% (SSP5-8.5) of global cropland could require new crop varieties to avoid yield loss from climate change by the end of the century. At low levels of warming (SSP1-2.6), 85% of currently cultivated land can draw from existing varieties to shift within an agro-ecological zone for adaptation. The assumptions on available varieties for adaptation have major impacts on the effectiveness of variety adaptation, which could more than half in SSP5-8.5. The results highlight that region-specific breeding efforts are required to allow for a successful adaptation to climate change.

Postmortem investigation of fatalities following vaccination with COVID-19 vaccines.

Thorough postmortem investigations of fatalities following vaccination with coronavirus disease 2019 (COVID-19) vaccines are of great social significance. From 11.03.2021 to 09.06.2021, postmortem investigations of 18 deceased persons who recently received a vaccination against COVID-19 were performed. Vaxzevria was vaccinated in nine, Comirnaty in five, Spikevax in three, and Janssen in one person. In all cases, full autopsies, histopathological examinations, and virological analyses for the severe acute respiratory syndrome coronavirus 2 were carried out. Depending on the case, additional laboratory tests (anaphylaxis diagnostics, VITT [vaccine-induced immune thrombotic thrombocytopenia] diagnostics, glucose metabolism diagnostics) and neuropathological examinations were conducted. In 13 deceased, the cause of death was attributed to preexisting diseases while postmortem investigations did not indicate a causal relationship to the vaccination. In one case after vaccination with Comirnaty, myocarditis was found to be the cause of death. A causal relationship to vaccination was considered possible, but could not be proven beyond doubt. VITT was found in three deceased persons following vaccination with Vaxzevria and one deceased following vaccination with Janssen. Of those four cases with VITT, only one was diagnosed before death. The synopsis of the anamnestic data, the autopsy results, laboratory diagnostic examinations, and histopathological and neuropathological examinations revealed that VITT was the very likely cause of death in only two of the four cases. In the other two cases, no neuropathological correlate of VITT explaining death was found, while possible causes of death emerged that were not necessarily attributable to VITT. The results of our study demonstrate the necessity of postmortem investigations on all fatalities following vaccination with COVID-19 vaccines. In order to identify a possible causal relationship between vaccination and death, in most cases an autopsy and histopathological examinations have to be combined with additional investigations, such as laboratory tests and neuropathological examinations.

Transmission of SARS-CoV-2 in northern Ghana: insights from whole-genome sequencing.

Following the detection of the first imported case of COVID-19 in the northern sector of Ghana, we molecularly characterized and phylogenetically analysed sequences, including three complete genome sequences, of severe acute respiratory syndrome coronavirus 2 obtained from nine patients in Ghana. We performed high-throughput sequencing on nine samples that were found to have a high concentration of viral RNA. We also assessed the potential impact that long-distance transport of samples to testing centres may have on sequencing results. Here, two samples that were similar in terms of viral RNA concentration but were transported from sites that are over 400 km apart were analyzed. All sequences were compared to previous sequences from Ghana and representative sequences from regions where our patients had previously travelled. Three complete genome sequences and another nearly complete genome sequence with 95.6% coverage were obtained. Sequences with coverage in excess of 80% were found to belong to three lineages, namely A, B.1 and B.2. Our sequences clustered in two different clades, with the majority falling within a clade composed of sequences from sub-Saharan Africa. Less RNA fragmentation was seen in sample KATH23, which was collected 9 km from the testing site, than in sample TTH6, which was collected and transported over a distance of 400 km to the testing site. The clustering of several sequences from sub-Saharan Africa suggests regional circulation of the viruses in the subregion. Importantly, there may be a need to decentralize testing sites and build more capacity across Africa to boost the sequencing output of the subregion.

Diffusion Tensor Imaging Color-Coded Maps: An Alternative to Tractography.

INTRODUCTION: White matter tracts can be observed using tractograms generated from diffusion tensor imaging (DTI). However, the dependence of these white matter tract images on subjective variables, including how seed points are placed and the preferred level of fractional anisotropy, introduces interobserver inconsistency and potential lack of reliability. We propose that color-coded maps (CCM) generated from DTI can be a preferred method for the visualization of important white matter tracts, circumventing bias in preoperative brain tumor resection planning. METHODS: DTI was acquired retrospectively in 25 patients with brain tumors. Lesions included 15 tumors of glial origin, 9 metastatic tumors, 2 meningiomas, and 1 cavernous angioma. Tractograms of the pyramidal tract and/or optic radiations, based on tumor location, were created by marking seed regions of interest using known anatomical locations. We compared the degree of tract involvement and white matter alteration between CCMs and tractograms. Neurological outcomes were obtained from chart reviews. RESULTS: The pyramidal tract was evaluated in 20/25 patients, the visual tracts were evaluated in 10/25, and both tracts were evaluated in 5/25. In 19/25 studies, the same patterns of white matter alternations were found between the CCMs and tractograms. In the 6 patients where patterns differed, 2 tractograms were not useful in determining pattern alteration; in the remaining 4/6, no practical difference was seen in comparing the studies. Two patients were lost to follow-up. Thirteen patients were neurologically improved or remained intact after intervention. In these, 10 of the 13 patients showed tumor-induced white matter tract displacement on CCM. Twelve patients had no improvement of their preoperative deficit. In 9 of these 12 patients, CCM showed white matter disruption. CONCLUSION: CCMs provide a convenient, practical, and objective method of visualizing white matter tracts, obviating the need for potentially subjective and time-consuming tractography. CCMs are at least as reliable as tractograms in predicting neurological outcomes after neurosurgical intervention.

Dynamic genome wide expression profiling of Drosophila head development reveals a novel role of Hunchback in retinal glia cell development and blood-brain barrier integrity.

Drosophila melanogaster head development represents a valuable process to study the developmental control of various organs, such as the antennae, the dorsal ocelli and the compound eyes from a common precursor, the eye-antennal imaginal disc. While the gene regulatory network underlying compound eye development has been extensively studied, the key transcription factors regulating the formation of other head structures from the same imaginal disc are largely unknown. We obtained the developmental transcriptome of the eye-antennal discs covering late patterning processes at the late 2nd larval instar stage to the onset and progression of differentiation at the end of larval development. We revealed the expression profiles of all genes expressed during eye-antennal disc development and we determined temporally co-expressed genes by hierarchical clustering. Since co-expressed genes may be regulated by common transcriptional regulators, we combined our transcriptome dataset with publicly available ChIP-seq data to identify central transcription factors that co-regulate genes during head development. Besides the identification of already known and well-described transcription factors, we show that the transcription factor Hunchback (Hb) regulates a significant number of genes that are expressed during late differentiation stages. We confirm that hb is expressed in two polyploid subperineurial glia cells (carpet cells) and a thorough functional analysis shows that loss of Hb function results in a loss of carpet cells in the eye-antennal disc. Additionally, we provide for the first time functional data indicating that carpet cells are an integral part of the blood-brain barrier. Eventually, we combined our expression data with a de novo Hb motif search to reveal stage specific putative target genes of which we find a significant number indeed expressed in carpet cells.