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Most neurons that make up the human brain are postmitotic, living and functioning for a very long time without renewal (see the Perspective by Lee). Bae et al. examined the genomes of single neurons from the prenatal developing human brain. Both the type of mutation and the rates of accumulation changed between gastrulation and neurogenesis. These early mutations could be generating useful neuronal diversity or could predispose individuals to later dysfunction. Lodato et al. also found that neurons take on somatic mutations as they age by sequencing single neurons from subjects aged 4 months to 82 years. Somatic mutations accumulated with increasing age and accumulated faster in individuals affected by inborn errors in DNA repair. Postmitotic mutations might only affect one neuron, but the accumulated divergence of genomes across the brain could affect function. Science , this issue p. 550 , p. 555 ; see also p. 521 Hundreds of oxidative damage–related somatic mutations per cell accumulate during early brain development. Somatic mosaicism in the human brain may alter function of individual neurons. We analyzed genomes of single cells from the forebrains of three human fetuses (15 to 21 weeks postconception) using clonal cell populations. We detected 200 to 400 single-nucleotide variations (SNVs) per cell. SNV patterns resembled those found in cancer cell genomes, indicating a role of background mutagenesis in cancer. SNVs with a frequency of >2% in brain were also present in the spleen, revealing a pregastrulation origin. We reconstructed cell lineages for the first five postzygotic cleavages and calculated a mutation rate of ~1.3 mutations per division per cell. Later in development, during neurogenesis, the mutation spectrum shifted toward oxidative damage, and the mutation rate increased. Both neurogenesis and early embryogenesis exhibit substantially more mutagenesis than adulthood.

The combination of family-based linkage analysis with high-throughput sequencing is a powerful approach to identifying rare genetic variants that contribute to genetically heterogeneous syndromes. Using parametric multipoint linkage analysis and whole exome sequencing, we have identified a gene responsible for microcephaly (MCP), severe visual impairment, intellectual disability, and short stature through the mapping of a homozygous nonsense alteration in a multiply-affected consanguineous family. This gene, DIAPH1, encodes the mammalian Diaphanous-related formin (mDia1), a member of the diaphanous-related formin family of Rho effector proteins. Upon the activation of GTP-bound Rho, mDia1 generates linear actin filaments in the maintenance of polarity during adhesion, migration, and division in immune cells and neuroepithelial cells, and in driving tangential migration of cortical interneurons in the rodent. Here, we show that patients with a homozygous nonsense DIAPH1 alteration (p.Gln778*) have MCP as well as reduced height and weight. diap1 (mDia1 knockout (KO))-deficient mice have grossly normal body and brain size. However, our histological analysis of diap1 KO mouse coronal brain sections at early and postnatal stages shows unilateral ventricular enlargement, indicating that this mutant mouse shows both important similarities as well as differences with human pathology. We also found that mDia1 protein is expressed in human neuronal precursor cells during mitotic cell division and has a major impact in the regulation of spindle formation and cell division.

Somatic mosaicism in the human brain may alter function of individual neurons. We analyzed genomes of single cells from the forebrains of three human fetuses (15 to 21 weeks post-conception) using clonal cell populations. We detected 200–400 single nucleotide variations (SNVs) per cell. SNV patterns resembled those found in cancer cell genomes, indicating a role of background mutagenesis in cancer. SNVs with a frequency of >2% in brain were shared with the spleen, revealing a pre-gastrulation origin. We reconstructed cell lineages for the first five post-zygotic cleavages and calculated a mutation rate of ~1.3 per division per cell. Later in development, during neurogenesis, the mutation spectrum shifted towards oxidative damage and the mutation rate increased. Both neurogenesis and early embryogenesis exhibit drastically more mutagenesis than adulthood.

The ventropallial excitatory neurons (ExNs) in the claustro-amygdalar complex and piriform cortex (PIR; part of paleocortex) form crucial reciprocal connections with the prefrontal cortex (PFC), integrating cognitive and sensory information that result in adaptive behaviors. Early-life disruptions in these circuits are linked to neuropsychiatric disorders, highlighting the importance of understanding their development. Our study uncovers that transcription factors SOX4, SOX11, and TFAP2D play a pivotal role in the development, identity, and PFC connectivity of these neurons. Using mouse models, we demonstrate that the absence of transcription factors SOX4 and SOX11 in post-mitotic ExNs dramatically reduces the size of the basolateral amygdala complex (BLC), claustrum, and PIR. SOX4 and SOX11 control BLC formation through direct regulation of Tfap2d expression. Cross-species analyses, including humans, identified conserved Tfap2d expression in developing ExNs of BLC, claustrum, paleocortex including PIR, and the associated transitional areas of the frontal, insular and temporal cortex. While the loss and haploinsufficiency of Tfap2d yield similar alterations in learned threat behaviors, differences emerge in the manifestation of Tfap2d dosage, particularly in terms of changes observed in BLC size and the connectivity pattern between the BLC and PFC. This underscores the significance of Tfap2d dosage in orchestrating developmental shifts in BLC-PFC connectivity and behavioral modifications reminiscent of symptoms of neuropsychiatric disorders. Together, these findings reveal key elements of a conserved gene regulatory network that shapes the development and function of crucial ventropallial ExNs and their PFC connectivity and offer insights into their evolution and alterations in neuropsychiatric disorders.

The hippocampal-entorhinal system is comprised of functionally distinct subregions collectively critical for cognition, and selectively vulnerable to aging and pathological processes. To gain insights into neuronal and non-neuronal populations within this system, we performed single-nucleus transcriptional profiling from five human hippocampal-entorhinal subregions. We found that transcriptomic diversity of excitatory neurons across these subregions reflected the molecular transition from three-layered archicortex to six-layered neocortex. Additionally, mRNA and protein for DCX, an immature neuron marker, were clearly detected in some cells, but not in dentate granule cells, the cell-type predicted to be generated in adult neurogenesis. We also found that previously functionally uncharacterized METTL7B was enriched in human and non-human primate neuronal subtypes less vulnerable to initial Alzheimer’s disease pathology. Proteomic and biochemical assays revealed METTL7B interacts with Alzheimer’s disease-related proteins, including APP, and its overexpression reduced amyloid-beta generation. These results reveal cell type-specific molecular properties relevant for hippocampal-entorhinal physiology and dysfunction.

The hippocampal-entorhinal system is comprised of functionally distinct subregions collectively critical for cognition, and selectively vulnerable to aging and pathological processes. To gain insights into neuronal and non-neuronal populations within this system, we performed single-nucleus transcriptional profiling from five human hippocampal-entorhinal subregions. We found that transcriptomic diversity of excitatory neurons across these subregions reflected the molecular transition from three-layered archicortex to six-layered neocortex. Additionally, mRNA and protein for DCX, an immature neuron marker, were clearly detected in some cells, but not in dentate granule cells, the cell-type predicted to be generated in adult neurogenesis. We also found that previously functionally uncharacterized METTL7B was enriched in human and non-human primate neuronal subtypes less vulnerable to initial Alzheimer's disease pathology. Proteomic and biochemical assays revealed METTL7B interacts with Alzheimer's disease-related proteins, including APP, and its overexpression reduced amyloid-beta generation. These results reveal cell type-specific molecular properties relevant for hippocampal-entorhinal physiology and dysfunction.

Croatia is among the most ecologically diverse and floristically rich countries in Europe, with a great variety of communities. The vegetation elaboration according to the standard central European method was initiated in Croatia at the beginning of the 20 century. In previous overviews of Croatian vegetation, the number of classes and alliances was underrepresented in relation to the country’s floristic richness. Furthermore, the level of knowledge and the amount of available data varied greatly among the various types of vegetation. The aims of this paper are mainly to compile a stabile syntaxonomic list of classes, orders and alliances dominated by vascular plants in Croatia and to adjust Croatian vegetation to the new European syntaxonomic system (EuroVegChecklist). It introduces a consistent description of high-rank syntaxa in Croatian. In conclusion, the vegetation of Croatia comprises 66 classes, 121 orders and 201 alliances. The number of syntaxa shows vegetation diversity that is rather high compared to most other European countries; this is related to the high floristic richness and endemism. The list points out the obvious problems and gaps in our knowledge of vegetation in Croatia and can serve as a baseline for the future vegetation studies.

The Žumberak and Samobor highlands are situated in the north-western part of Croatia where the characteristics of the Dinarides, the Alps and the Pannonian Plain meet. The greater part of the area is occupied by beech forests. The aim of the study was to determine the syntaxonomic affiliation of these forest communities, and to explore their floristic and main ecological features. Numerical analyses of floristic compositions were conducted on a data-set consisting of 144 new relevés and 99 relevés from the existing literature. Relevés were made following the standard Braun-Blanquet method. For descriptions of ecological conditions Ellenberg’s indicator values were used. Six plant associations and two subassociations of beech forests were established in and alliances. The higher altitudes of the studied area are occupied by ass. , whereas the lower altitudes are occupied by ass. and . Ass. spreads on southern slopes and ridges, whereas ass. occurs in ditches and on northern slopes. In the warmer habitats with shallow soils on a dolomite base ass. occurred. A small part of the area is characterized by silicate substrate which is occupied by ass. and

The article deals with wet meadow plant communities of the alliance Trifolion pallidi that appear on the periodically inundated or waterlogged sites on the riverside terraces or gentle slopes along watercourses. These plant communities are often endangered by inappropriate hydrological interventions or management practices. All available vegetation plots representing this vegetation type were collected, organized in a database, and numerically elaborated. This vegetation type appears in the southeastern part of the Pannonian Plain, which is still under the influence of the Mediterranean climate; its southern border is formed by southern outcrops of the Pannonian Plain and its northern border coincides with the influence of the Mediterranean climate (line Slavonsko Gorje-Fruška Gora-Vršačke Planine). Numerical analysis established four plant associations—Trifolio pallidi–Alopecuretum pratensis, Ventenato dubii–Trifolietum pallidi, Ranunculo strigulosi–Alopecuretum pratensis, and Ornithogalo pyramidale–Trifolietum pallidi. Each association was elaborated in detail: diagnostic plant species, nomenclature, geographical distribution, climatic and ecological conditions, and possible division into subassociations. Results are presented in a distribution map, figures resulting from numerical analysis, and a synoptic table. The hydrological gradient was found as the most important factor shaping the studied plant communities. The article also brings new field data on this vegetation type, which has not been sampled for decades and is in process of evaluation to be included as a special habitat type in the Habitat Directive.

QUESTIONS: How does the floristic composition of plant species of meadows and mesic pastures vary along a broad geographical gradient in the NW Balkans? How does the current phytosociological classification of the Molinio‐Arrhenatheretea vegetation differ among the NW Balkan countries? LOCATION: NW Balkans (Slovenia, Croatia, Bosnia and Herzegovina, Serbia). METHODS: 3635 relevés originally assigned to the class Molinio‐Arrhenatheretea were classified with a beta flexible method, and the crispness of classification was checked. DCA ordination with Pignatti indicator values and climate data were applied to show the influence of site conditions on species composition. RESULTS: The classification was best interpreted at the level of 13 clusters, but could also be interpreted at the level of three groups of clusters. The first division was according to geography and climate: the first and third groups were concentrated in the NW part, while the second was restricted to the eastern part of the study area. The most important variable was site moisture, followed by nutrients and altitude, which corresponded with a west–east direction. The first group was very diverse and included communities on the wettest and most nutrient‐rich sites (Potentillion anserinae, Cynosurion cristati, Calthion palustris, Molinion caeruleae, Molinio‐Hordeion). The second group comprised mesophilous continental grasslands (Trifolio‐Ranunculion pedati, Trifolion pallidi, Trifolion resupinati), while the third group consisted of grasslands from regions with abundant precipitation (Arrhenatherion elatioris, Deschampsion cespitosae, Pancicion serbicae, Triseto flavescentis‐Polygonion bistortae). CONCLUSIONS: Our analysis can be used to unify different phytosociological classifications in different countries, also showing the transitional forms of well‐known Central European vegetation types that have a different floristic composition and ecology in the Balkans. This knowledge will enable classification of the same vegetation types in neighbouring Balkan countries that are less studied.