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Ribeiro Gomes, A. R.

Publications and source records attributed to Ribeiro Gomes, A. R..

4 recordsLinked to original sources

A cross-species protocol for ultrasound-guided intrauterine injections across gestation

This step-by-step protocol provides a cross-species, non-surgical approach that enables prenatal gene delivery to the developing nervous system in rats and marmosets. Under transabdominal ultrasound guidance, intracerebroventricular injection of recombinant adeno-associated virus vectors into the fetal brain achieves robust and long-term transduction from prenatal stages into adulthood. This approach can be adapted to other species and target sites outside nervous system, enabling safe and selective intrauterine manipulation and the generation of diverse experimental models for basic and preclinical research. For complete details on the use and execution of this protocol, please refer to Ribeiro Gomes et al (2026)1. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/737050v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@696364org.highwire.dtl.DTLVardef@fc3c7forg.highwire.dtl.DTLVardef@1e7c7caorg.highwire.dtl.DTLVardef@1edcef0_HPS_FORMAT_FIGEXP M_FIG C_FIG Before you beginExperimental procedures during gestation allow researchers to study developmental processes, including how manipulations of the fetus and its intrauterine environment influence biological outcomes. Ultrasound imaging guidance greatly facilitates such interventions by providing safe and targeted access to fetal compartments, including for prenatal gene delivery to developing neural cell populations. Critically, delivery of recombinant adeno-associated viruses (rAAVs) into the cerebrospinal fluid (CSF) of developing animals enables widespread gene transfer across the brain. The efficiency and distribution of transduction are strongly influenced by developmental stage, making the timing of delivery an important experimental variable. In altricial species such as mice, major developmental processes, including cortical lamination and the establishment of long-range connections, begin prenatally but continue throughout early postnatal life. In primates, however, development is more advanced at birth, and many equivalent developmental events are shifted to the prenatal period. Consequently, developmental stages that can be targeted postnatally in mice require prenatal access in primates. Here, we present a step-by-step protocol for ultrasound-guided fetal intracerebroventricular viral injection (FIVI) of rAAV in marmosets (Callithrix jacchus) and rats (Rattus norvegicus). The procedure was initially developed and optimized in rats before being translated to marmosets, small New World primates that share key developmental, anatomical, and functional characteristics with humans. Together, these models illustrate the cross-species applicability of the approach, while providing gene delivery strategies for both a genetically tractable rodent model and a translationally relevant nonhuman primate. FIVI enables broad gene transfer and stable, long-term transgene expression in wild type animals, facilitating the generation of complementary quasi-transgenic models for research and translational applications from prenatal development through adulthood.

neuroscience↗

Targeted gene transfer into developmentally defined cell populations of the primate brain

The primate brain possesses unique physiological and developmental features whose systematic investigation is hampered by a paucity of transgenic germline models and tools. Here, we present a minimally invasive method to introduce transgenes widely across the primate cerebral cortex using ultrasound-guided fetal intracerebroventricular viral injections (FIVI). This technique enables rapid-onset and long-lasting transgene expression following the delivery of recombinant adeno-associated viruses (rAAVs). By adjusting the gestational timing of injections, viral serotypes, and transcriptional regulatory elements, rAAV FIVI allows for systematic targeting of specific cell populations. We demonstrate the versatility of this method through restricted laminar expression in the cortex, Cre-dependent targeting of neurons, CRISPR-based gene editing, and labeling of peripheral somatosensory and retinal pathways. By mimicking key desirable features of germline transgenic models, this efficient and targeted method for gene transfer into the fetal primate brain opens new avenues for experimental and translational neuroscience across the lifespan.

neuroscience↗

Predictability of cortical-cortical connections in the mammalian brain

Despite a five-order magnitude range in size, the mammalian brain exhibits many shared anatomical and functional characteristics that should translate into cortical network commonalities. Here we develop a framework employing machine learning to quantify the degree of predictability of the weighted interareal cortical matrix. Data were obtained with retrograde tract-tracing experiments supplemented by projection length measurements. Using this framework with consistent and edge-complete empirical datasets in the macaque and mouse cortex, we show that there is significant amount of predictability embedded in the interareal cortical networks of both species. At the binary level, links are predictable with an Area Under the ROC curve of at least 0.8 for the macaque. At the weighted level, strengths of the medium and strong links are predictable with at least 85-90% accuracy in mouse and 70-80% in macaque, whereas weak links are not predictable in either species. These observations suggest that the formation and evolution of the cortical network at the mesoscale is to a large extent, rule-based, motivating further research on the architectural invariants of the cortical connectome.

neuroscience↗

Refinement of the primate corticospinal pathway during prenatal development

Perturbation of the developmental refinement of the corticospinal pathway leads to motor disorders. In non-primates developmental refinement is well documented, however in primates invasive investigations of the developing corticospinal pathway have been confined to neonatal and postnatal stages when refinement is relatively modest.\n\nHere, we investigated the developmental changes in the distribution of corticospinal projection neurons in cynomolgus monkey. Injections of retrograde tracer at the cervical levels of the spinal cord at embryonic day (E) 95 and E105 show that (i) areal distribution of back-labeled neurons is more extensive than in the neonate and dense labeling is found in prefrontal, limbic, temporal and occipital cortex; (ii) distributions of contra- and ipsilateral projecting corticospinal neurons are comparable in terms of location and numbers of labeled neurons, in contrast to the adult where the contralateral projection is an order of magnitude higher than the ipsilateral projection. Findings from one largely restricted injection suggest a hitherto unsuspected early innervation of the gray matter.\n\nIn the fetus there was in addition dense labeling in the central nucleus of the amygdala, the hypothalamus, the subthalamic nucleus and the adjacent region of the zona incerta, subcortical structures with only minor projections in the adult control.

neuroscience↗