Kcnj2 regulates electrical activity-induced gene networks in embryonic mouse palate shelves.

Cleft palate interferes with eating, drinking, breathing, and speech, causing significant human suffering. Fetal exposure to many medications that target ion channels increases the incidence of cleft palate. Cleft palate could be prevented by understanding how ion channels contribute to palatal development.

In mice, discrete odors can selectively promote the neurogenesis of sensory neuron subtypes that they stimulate.

In mammals, olfactory sensory neurons (OSNs) are born throughout life, ostensibly solely to replace neurons lost turnover or injury. This assumption follows from the hypothesis that olfactory neurogenesis is stochastic with respect to neuron subtype, as defined by the single odorant receptor that each neural precursor stochastically chooses out of hundreds of possibilities. This assumption is challenged, however, by recent findings that the birthrates of a fraction of OSN subtypes are selectively reduced by olfactory deprivation.

Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2.

The meninges act as a regulator of brain development by secreting ligands that act on neural cells to regulate neurogenesis and neuronal migration. Meningeal-derived retinoic acid (RA) promotes neocortical neural progenitor cell cycle exit; however, the underlying molecular mechanism is unknown. Here, we used spatial transcriptomics and profiling of retinoic acid receptor α (RARα) DNA binding in Foxc1-mutant embryos that lack meninges-derived signals to identify potential neurogenic transcriptional mechanisms of RA signaling in telencephalic neural progenitors.

Leptomeningeal Neural Organoid Fusions as Models to Study Meninges-Brain Signaling.

Neural organoids derived from human-induced pluripotent stem cells (iPSCs) provide a model to study the earliest stages of human brain development, including neurogenesis, neural differentiation, and synaptogenesis. However, neural organoids lack supportive tissues and some non-neural cell types that are key regulators of brain development. Neural organoids have instead been cocultured with non-neural structures and cell types to promote their maturation and model interactions with neuronal cells.

The pericardium forms as a distinct structure during heart formation.

The heart integrates diverse cell lineages into a functional unit, including the pericardium, a mesothelial sac that supports heart movement, homeostasis, and immune responses. However, despite its critical roles, the developmental origins of the pericardium remain uncertain due to disparate models. Here, using live imaging, lineage tracking, and single-cell transcriptomics in zebrafish, we find the pericardium forms within the lateral plate mesoderm from dedicated anterior mesothelial progenitors and distinct from the classic heart field.

scMultiome analysis identifies a single caudal hindbrain compartment in the developing zebrafish nervous system.

Background: A key step in nervous system development involves the coordinated control of neural progenitor specification and positioning. A long-standing model for the vertebrate CNS postulates that transient anatomical compartments - known as neuromeres - function to position neural progenitors along the embryonic anteroposterior neuraxis. Such neuromeres are apparent in the embryonic hindbrain - that contains six rhombomeres with morphologically apparent boundaries - but other neuromeres lack clear morphological boundaries and have instead been defined by different criteria, such as differences in gene expression patterns and the outcomes of transplantation experiments.

Bulk and single-cell transcriptome datasets of the mouse fetal and adult rete ovarii and surrounding tissues.

The rete ovarii (RO) is an epithelial structure that arises during development in close proximity to the ovary and persists throughout adulthood. However, the functional significance of the RO remains elusive, and it is absent from recent discussions of female reproductive anatomy. The RO comprises three regions: the intraovarian rete within the ovary, the extraovarian rete in the periovarian tissue, and the connecting rete linking the two.

In mice, discrete odors can selectively promote the neurogenesis of sensory neuron subtypes that they stimulate.

In mammals, olfactory sensory neurons (OSNs) are born throughout life, ostensibly solely to replace neurons lost turnover or injury. This assumption follows from the hypothesis that olfactory neurogenesis is stochastic with respect to neuron subtype, as defined by the single odorant receptor that each neural precursor stochastically chooses out of hundreds of possibilities. This assumption is challenged, however, by recent findings that the birthrates of a fraction of OSN subtypes are selectively reduced by olfactory deprivation.

Leptomeningeal Neural Organoid (LMNO) Fusions as Models to Study Meninges-Brain Signaling.

Neural organoids derived from human induced pluripotent stem cells (iPSCs) provide a model to study the earliest stages of human brain development, including neurogenesis, neural differentiation, and synaptogenesis. However, neural organoids lack supportive tissues and some non-neural cell types that are key regulators of brain development. Neural organoids have instead been co-cultured with non-neural structures and cell types to promote their maturation and model interactions with neuronal cells.

Leptomeningeal Neural Organoid (LMNO) Fusions as Models to Study Meninges-Brain Signaling.

Neural organoids derived from human induced pluripotent stem cells (iPSCs) provide a model to study the earliest stages of human brain development, including neurogenesis, neural differentiation, and synaptogenesis. However, neural organoids lack supportive tissues and some non-neural cell types that are key regulators of brain development. Neural organoids have instead been co-cultured with non-neural structures and cell types to promote their maturation and model interactions with neuronal cells.

Transcriptome analysis of the mouse fetal and adult rete ovarii and surrounding tissues.

The rete ovarii (RO) is an epithelial structure that arises during fetal development in close proximity to the ovary and persists throughout adulthood in mice. However, the functional significance of the RO remains elusive, and it has been absent from recent discussions of female reproductive anatomy. The RO comprises three distinct regions: the intraovarian rete (IOR) within the ovary, the extraovarian rete (EOR) in the periovarian tissue, and the connecting rete (CR) linking the EOR and IOR.

scMultiome analysis identifies embryonic hindbrain progenitors with mixed rhombomere identities.

Rhombomeres serve to position neural progenitors in the embryonic hindbrain, thereby ensuring appropriate neural circuit formation, but the molecular identities of individual rhombomeres and the mechanism whereby they form has not been fully established. Here, we apply scMultiome analysis in zebrafish to molecularly resolve all rhombomeres for the first time. We find that rhombomeres become molecularly distinct between 10hpf (end of gastrulation) and 13hpf (early segmentation).

Metformin Disrupts Signaling and Metabolism in Fetal Hepatocytes.

Unlabelled: Metformin is used by women during pregnancy to manage diabetes and crosses the placenta, yet its effects on the fetus are unclear. We show that the liver is a site of metformin action in fetal sheep and macaques, given relatively abundant OCT1 transporter expression and hepatic uptake following metformin infusion into fetal sheep. To determine the effects of metformin action, we performed studies in primary hepatocytes from fetal sheep, fetal macaques, and juvenile macaques.

Formation and function of the meningeal arachnoid barrier around the developing mouse brain.

The arachnoid barrier, a component of the blood-cerebrospinal fluid barrier (B-CSFB) in the meninges, is composed of epithelial-like, tight-junction-expressing cells. Unlike other central nervous system (CNS) barriers, its' developmental mechanisms and timing are largely unknown. Here, we show that mouse arachnoid barrier cell specification requires the repression of Wnt-β-catenin signaling and that constitutively active β-catenin can prevent its formation.

scMultiome analysis identifies embryonic hindbrain progenitors with mixed rhombomere identities.

Rhombomeres serve to position neural progenitors in the embryonic hindbrain, thereby ensuring appropriate neural circuit formation, but the molecular identities of individual rhombomeres and the mechanism whereby they form have not been fully established. Here we apply scMultiome analysis in zebrafish to molecularly resolve all rhombomeres for the first time. We find that rhombomeres become molecularly distinct between 10hpf (end of gastrulation) and 13hpf (early segmentation).

Single cell sequencing of the mouse anterior palate reveals mesenchymal heterogeneity.

Background: Cleft palate is one of the most prevalent birth defects. Mice are useful for studying palate development because of their morphological and genetic similarities to humans. In mice, palate development occurs between embryonic days (E)11.

The regenerating skeletal muscle niche drives satellite cell return to quiescence.

Skeletal muscle stem cells, or satellite cells (SCs), are essential to regenerate and maintain muscle. Quiescent SCs reside in an asymmetric niche between the basal lamina and myofiber membrane. To repair muscle, SCs activate, proliferate, and differentiate, fusing to repair myofibers or reacquiring quiescence to replenish the SC niche.

Professionalism development and assessment in the pre-registration pharmacist placement in England: transformative moments and maturation periods.

Objectives: Development of new patient-facing roles for pharmacists and reports of poor patient care in the UK has led to questions concerning how pharmacists develop professionalism. This study explored how professionalism is developed and assessed during the post-graduation year in practice or pre-registration placement. The perspectives of two staff at the professional regulator UK (General Pharmaceutical Council), eight service users, seven pre-registration trainees, and 12 pre-registration tutors were recruited.

Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma.

The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood.

Single-cell transcriptional analysis of human endothelial colony-forming cells from patients with low VWF levels.

von Willebrand factor (VWF) plays a key role in normal hemostasis, and deficiencies of VWF lead to clinically significant bleeding. We sought to identify novel modifiers of VWF levels in endothelial colony-forming cells (ECFCs) using single-cell RNA sequencing (scRNA-seq). ECFCs were isolated from patients with low VWF levels (plasma VWF antigen levels between 30 and 50 IU/dL) and from healthy controls.

Busting myths in online education: Faculty examples from the field.

The shift in learning environments due to the COVID-19 pandemic necessitates a closer look at course design, faculty approaches to teaching, and student interaction, all of which may predict learner achievement and satisfaction. Transitioning to an online environment requires the reinvention, reimagining, and applying of "e-flavors" of general learning theory. With this shift to online learning comes the opportunity for misunderstandings and "myths" to occur, which may stand in the way of faculty embracing online learning and fully realizing its potential.

Temporal single-cell transcriptomes of zebrafish spinal cord pMN progenitors reveal distinct neuronal and glial progenitor populations.

Ventral spinal cord progenitor cells, which express the basic helix loop helix transcription factor Olig2, sequentially produce motor neurons and oligodendrocyte precursor cells (OPCs). Following specification some OPCs differentiate as myelinating oligodendrocytes while others persist as OPCs. Though a considerable amount of work has described the molecular profiles that define motor neurons, OPCs, and oligodendrocytes, less is known about the progenitors that produce them.

Recognising the elephant in the room: Foundation doctors and anticipatory care planning.

Anticipatory/advance care planning (ACP) conversations are often known to be challenging and should be undertaken sensitively. A qualitative service evaluation was undertaken with the elderly care department at The Leeds Teaching Hospitals NHS Trust by medical students to explore the thoughts and experiences of foundation doctors. ACP discussions include consideration of future treatment options and preferences; however, foundation doctors were not confident to discuss issues beyond resuscitation status.

Prdm8 regulates pMN progenitor specification for motor neuron and oligodendrocyte fates by modulating the Shh signaling response.

Spinal cord pMN progenitors sequentially produce motor neurons and oligodendrocyte precursor cells (OPCs). Some OPCs differentiate rapidly as myelinating oligodendrocytes, whereas others remain into adulthood. How pMN progenitors switch from producing motor neurons to OPCs with distinct fates is poorly understood.