Biology subjects

Escobar, L.

Publications and source records attributed to Escobar, L..

5 recordsLinked to original sources

bioRxiv2025

A dual genetic constraint underlies the conservation of early brains in vertebrates.

As the body plan, the embryonic brain bauplan reflects the shared features of vertebrate brains. Yet, disagreements among sparse histogenetic frameworks have undermined the bauplans power to trace homologies. Here, we generate and integrate five vertebrate single-cell multi-omic atlases of early embryonic brains, revealing a conserved cellular blueprint that defines equivalent progenitor domains across species. Our cellular neuromeric model provides an unified and unbiased framework for the vertebrate brain bauplan and revises the regionalisation of the prosencephalon, refining its molecular boundaries and developmental relationships. Furthermore, cross-species gene-network analyses expose regulatory complexity beyond classical neuromeric patterning, resolving networks into modules aligned with regional cell types or cell class (progenitor/neuron). Evolutionarily, two main developmental constraints emerge: brain bauplan genes, early essential for regional identity, and pleiotropic stemness gene modules, indispensable across all proliferating cells. In turn, later development displays tissue-specific and less essential modules, explaining its rapid divergence into species-specific features. Together, these findings reveal a dual evolutionary constraint--neuromeric identity and pleiotropic stemness--that underlies the conservation of early vertebrate brains. This duality explains how deeply conserved regulatory architectures coexist with evolutionary flexibility to develop into the immense diversity of vertebrate nervous systems. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/684766v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@a337a2org.highwire.dtl.DTLVardef@19987adorg.highwire.dtl.DTLVardef@9a9394org.highwire.dtl.DTLVardef@4ef279_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2025

Divergent Effects of APOE3 and APOE4 Human Astrocytes on Key Alzheimer's Disease Hallmarks in Chimeric Mice

Despite strong evidence supporting that both astrocytes and apolipoprotein E (APOE) play crucial roles in the pathogenesis and progression of Alzheimers disease (AD), the impact of astrocytes carrying different APOE variants on key AD pathological hallmarks remains largely unknown. To explore such effects in a human relevant context, we generated a chimeric model of AD. We transplanted isogenic APOE3 or APOE4 human induced pluripotent stem cell (hiPSC)-derived astrocyte progenitors into neonatal brains of AD model mice. We show that at five to six months after transplantation, transplanted cells have differentiated into mature astrocytes (h-astrocytes) that often integrate in upper layers of one cortical hemisphere. APOE3 and APOE4 h-astrocytes differentially express and secrete the APOE protein, which binds to A{beta} plaques with an isoform-dependent affinity. Remarkably, APOE3 h-astrocytes ameliorate A{beta} pathology, Tau pathology and neuritic dystrophy. In contrast, APOE4 h-astrocytes aggravate these AD processes. Moreover, APOE3 and APOE4 h-astrocytes modulate microglia responses to A{beta} pathology in opposite ways. APOE4 h-astrocytes enhance microglia clustering around A{beta} plaques and exacerbate DAM state whereas APOE3 h-astrocytes reduce microglia clustering and induce a more homeostatic state on plaque-associated microglia. These findings highlight a critical contribution of h-astrocytes not only to A{beta} pathology but also to other key AD hallmarks in chimeric mice. In addition, our findings reveal that h-astrocytes with different APOE variants and the different forms of APOE they secrete have a crucial role in AD progression.

neuroscience↗

bioRxiv2024

Evolutionary convergence of sensory circuits in the pallium of amniotes

The amniote pallium contains sensory circuits structurally and functionally equivalent, yet their evolutionary relationship remains unresolved. Our study employs birthdating analysis, single-cell RNA and spatial transcriptomics, and mathematical modeling to compare the development and evolution of known pallial circuits across birds (chick), lizards (gecko) and mammals (mouse). We reveal that neurons within these circuits stations are generated at varying developmental times and brain regions across species, and found an early developmental divergence in the transcriptomic progression of glutamatergic neurons. Together, we show divergent developmental and evolutionary trajectories in the pallial cell types of sauropsids and mammals. Our research highlights significant differences in circuit construction rules among species and pallial regions. Interestingly, despite these developmental distinctions, the sensory circuits in birds and mammals appear functionally similar, which suggest the convergence of high-order sensory processing across amniote lineages.

developmental biology↗

bioRxiv2023

BirthSeq, a new method to isolate and analyze dated cells from any tissue in vertebrates

Embryonic development is a complex and dynamic process that unfolds over time and involves the production of increasing numbers of cells, as well as the diversification of different cell types. The impact of developmental time on the formation of the central nervous system is well-documented, with evidence showing that time plays a critical role in establishing the identity of neuronal subtypes. However, the study of how time translates into genetic instructions driving cell fate is limited by the scarcity of suitable experimental tools. We introduce BirthSeq, a new method for isolating and analyzing cells based on their birth date. This innovative technique allows for in vivo labeling of cells, isolation via FACS, and analysis using high-throughput techniques. We demonstrate the effectiveness of BirthSeq for single-cell RNA sequencing and novel spatially resolved transcriptomic approaches in brain development across three vertebrate species (mouse, chick, and gecko). Overall, BirthSeq provides a versatile tool for studying any tissue in any vertebrate organism, helping to fill the necessity in developmental biology research by targeting cells and their temporal cues. SUMMARY STATEMENTBirthSeq allows the isolation and investigation of alive cells according to their birthdate, in any kind of tissue and vertebrate species.

developmental biology↗

bioRxiv2019

Spatial distribution and spread potential of sixteen Leptospira serovars in a subtropical region of Brazil

Leptospirosis is a bacterial disease that represents a major problem in animal and public health due to its high prevalence and widespread distribution. This zoonotic disease is most prevalent in tropical environments where conditions favor pathogen survival. The ecological preferences of Leptospira serovars are poorly understood, limiting our knowledge of where and when outbreaks can occur, which may result in misinformed prevention and control plans. While the disease can occur consistently in time and space in tropical regions, research on the ecology of Leptospirosis remains limited in subtropical regions. This research gap regarding Leptospira ecology brings public and veterinary health problems, impacting local economies. To fill this gap of knowledge, we propose to assess geographic and ecological features among Leptospira serovars in a subtropical area of Brazil where Leptospirosis is endemic to (i) highlight environmental conditions that facilitate or limit Leptospira spread and survival and (ii) reconstruct its geographical distribution. An ecological niche modeling framework was used to characterize and compare Leptospira serovars in both geographical and environmental space. Our results show that, despite the geographic overlap exhibited by the different serovars assessed, we found ecological divergence among their occupied ecological niches. Ecological divergences were expressed as ranges of potential distributions and environmental conditions found suitably by serovar, being Sejroe the most asymmetric. Most important predictors for the potential distribution of most serovars were soil pH (31.7%) and landscape temperature (24.2%). Identification of environmental preferences will allow epidemiologists to better infer the presence of a serovar based on the environmental characteristics of regions rather than inferences based solely on historical epidemiological records. Including geographic and ecological ranges of serovars also may help to forecast transmission potential of Leptospira in public health and the food animal practice.

epidemiology↗