Normal Migration Research Articles

Cancer Cell-Selective Inhibition of Migration by Styrenic Catiomer Emulsions.

Cancer metastasis remains the most formidable cause of mortality and morbidity in cancer patients. Developing an effective and economical method toward cancer antimetastatic strategy demands immediate attention in anticancer therapy. Herein, we followed a cost-effective greener method for preparing a small family of amphiphilic catiomers with varied styrene content (45, 63, and 83%), which revealed the unique potential of promoting normal cell migration while retarding cancer metastasis. The styrenic polymers formed micellar self-assembly in aqueous phase and exhibited a cationic charge. Polymers were quite nontoxic up to 200 μg/mL concentration toward human embryonic kidney cell HEK293 as well as human, triple negative breast cancer cell MDAMB-231, mouse melanoma cell B16F10, and human oral squamous carcinoma cell FaDu. Confocal imaging and fluorescence activated cell sorting (FACS) showed effective incorporation of polymers within cells. Interestingly, the polymer-treated HEK293 cells underwent prominent wound healing in scratch assay. However, the as-synthesized polymer-treated cancer cells resisted migration as analyzed from the scratch assay. A mechanistic study using immunoblotting assay established upregulation of migratory proteins vimentin and TGF-β and downregulation of E-cadherin in normal HEK293 cells. Remarkably, this trend was completely reversed in cancer cell MDAMB-231. This study describes the extraordinary potential of styrenic catiomers as wound healers for normal cells while inhibiting cancer metastasis.

First telemetry insights into the movements and vertical habitat use of megamouth shark (Megachasma pelagios) in the northwest Pacific

The megamouth shark (Megachasma pelagios) is one of the ocean's largest and most enigmatic elasmobranchs, with only a few hundred individuals ever recorded. Most of what is known about the species comes from rare fishery bycatch, stranding, or sighting events, precluding an in-depth understanding of its movement ecology. Here, we report the results from three megamouth sharks outfitted with pop-up satellite archival transmitting tags to assess the species' horizontal and vertical movement patterns. Deployments of 12, 58, and 244 d in duration provided the first direct evidence of multi-month fidelity to the waters east of Taiwan and seasonal movement out of the region. Depth and temperature data revealed a pattern of normal diel vertical migration, with the majority of the day spent in the mesopelagic zone and night in the epipelagic. Vertical habitat use suggests potential behavioral thermoregulation and was consistent with tracking of migrating mesopelagic prey across diel periods. We discuss the specialized analytical methods needed to reconstruct the spatial habitat use of deep-diving megamouth shark from tag sensor measurements of the magnetic field, as well as avenues for future research on this understudied megaplanktivore.

Unraveling the cellular mechanisms of tissue regeneration based on colloidal supraball bio-adhesives

Spherical aggregates of biocompatible mesoporous silica nanoparticles, known as supraballs (SBs), have been proposed as promising tissue adhesives, offering enhanced adhesion energy owing to their high specific surface area. Herein, we investigated the wound-healing mechanism of SBs achieved through nano-bridging at a cellular level. Lap shear tests on porcine skin exhibited improved wet adhesion as SB concentration increased. At 10 wt%, the adhesion strength reached approximately 37 kPa, surpassing that of fibrin glue (∼26 kPa). Hemocompatibility assessments showed non-hemolytic effects for both silica microparticles and SBs. In addition, SBs were validated to be biocompatible, exhibiting low immunogenicity, normal cell proliferation and migration, and degradability in cell media. In vivo results demonstrated that SB-treated wounds displayed accelerated wound closure, accompanied by earlier angiogenesis and low immune response, underscoring the potential of SBs as an effective tissue binder. Further investigation of the healing mechanism was conducted by analyzing differentially expressed genes in cells representing epidermal and dermal areas, revealing notable distinctions between control and SB-treated samples. These variations are associated with cellular behavior and microvascular endothelial cell and keratinocyte proliferation. Taken together, these findings indicate that SBs have the capability to serve as efficient tissue adhesives.

Human Malformed Perinatal Anthropological Crania Contribute to New Insight in the Extension of Bone Malformations in Cranial Development

Introduction We describe five abnormal crania which may provide more diagnostic data for assessment of abnormal crania in newborns. Methods Five malformed perinatal crania from the Saxtorphian Collection are described using published prenatal abnormal cranial development criteria. These malformations were compared to normal cranial development arising from the migration of neural crest cells. Visual and photographic investigations were performed. Results The malformed crania were occipital encephalocele, holoprosencephaly, anencephaly, and two without a recognizable diagnosis. The anthropological crania were malformed in the same regions as formerly observed in fetal pathology. These regions were comparable to fields formed during normal cell migration from the neural crest. This has seemingly not previously been demonstrated. One undiagnosed cranium may represent a Treacher Collins syndrome (Case 3). The other undiagnosed cranium (Case 4) could be from a scaphocephalic specimen. Discussion Sharp borderlines between malformed and non-malformed regions in cranial syndromes may enable improvement in diagnostics.

Role of steroid hormones in the maintenance of focal adhesions in bovine oviductal epithelial cells

The oviduct, the organ of the female reproductive system where fertilization and early embryonic development occur, provides an optimal environment for the final maturation of oocytes, storage, and sperm capacitation and transport of gametes and embryos. During the estrous cycle, the oviduct is affected by ovarian sex hormones, resulting in changes aimed at maintaining an appropriate microenvironment. Normal cell migration is tightly regulated, its role being essential for the development and maintenance of organ and tissue functions as well as for regeneration following injury. Due to their involvement in focal contact formations, focal adhesion kinase (PTK2) and paxillin (PXN) are key proteins in the study of cell migration and adhesion. The objective of this work was to compare the expression of PTK2 and PXN in oviductal cells along the estrous cycle and to determine if their expression is regulated by the presence of 17-β estradiol (E2) and/or progesterone (P4). No transcripts of PTK2 or of PXN were detected in cells corresponding to the luteal phase. Additionally, hormonal stimulation experiments on bovine oviductal cell cultures (BOECs) were carried out, where P4 inhibited the expression of both genes. Migration assays demonstrated that P4 reduced BOECs migration capacity. P4 treatment also reduced cell adhesion, while E2 increased the number of adhered cells. In conclusion, the presence of E2 and P4 regulates the expression of genes involved in the formation of focal contacts and modifies the migration and adhesion of BOECs. Understanding the effect of steroid hormones on BOECs is critical to grasp the impact of steroid control on oviductal function and its contribution to establishing successful pregnancies.

The Role of Hyperexcitable Existing Granule Cells in Seizure-Induced Ectopic Granule Cells

In adult neurogenesis, where new functional neurons are generated from precursor cells, certain neurological conditions like seizures can disrupt the normal production, migration, and integration of these neurons. This disruption is characterized by ectopic granule cells (GCs) appearing in locations other than the granule cell layer, particularly following seizure-induced neurogenesis. These ectopic cells form abnormal connections and contribute to the hyperexcitability of hippocampal circuits. Although the precise molecular mechanisms behind this phenomenon remain unclear, the interplay between hyperexcitable old GCs and ectopic seizure-induced GCs is a critical factor in understanding epileptic pathology. This research proposal focuses on the hypothesis that seizure-induced neuroblasts migrate as expected but fail to connect with old GCs due to heightened excitability, resulting in abnormal connections in incorrect locations. This investigation seeks to shed light on this complex interplay and its implications for epilepsy and potential therapeutic targets.

Unexpected Differences in the Speed of Non-Malignant versus Malignant Cell Migration Reveal Differential Basal Intracellular ATP Levels

Cellular locomotion is required for survival, fertility, proper embryonic development, regeneration, and wound healing. Cell migration is a major component of metastasis, which accounts for two-thirds of all solid tumor deaths. While many studies have demonstrated increased energy requirements, metabolic rates, and migration of cancer cells compared with normal cells, few have systematically compared normal and cancer cell migration as well as energy requirements side by side. Thus, we investigated how non-malignant and malignant cells migrate, utilizing several cell lines from the breast and lung. Initial screening was performed in an unbiased high-throughput manner for the ability to migrate/invade on collagen and/or Matrigel. We unexpectedly observed that all the non-malignant lung cells moved significantly faster than cells derived from lung tumors regardless of the growth media used. Given the paradigm-shifting nature of our discovery, we pursued the mechanisms that could be responsible. Neither mass, cell doubling, nor volume accounted for the individual speed and track length of the normal cells. Non-malignant cells had higher levels of intracellular ATP at premigratory-wound induction stages. Meanwhile, cancer cells also increased intracellular ATP at premigratory-wound induction, but not to the levels of the normal cells, indicating the possibility for further therapeutic investigation.

Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System Development.

The enteric nervous system (ENS) is principally derived from vagal neural crest cells that migrate caudally along the entire length of the gastrointestinal tract, giving rise to neurons and glial cells in two ganglionated plexuses. Incomplete migration of enteric neural crest-derived cells (ENCDC) leads to Hirschsprung disease, a congenital disorder characterized by the absence of enteric ganglia along variable lengths of the colorectum. Our previous work strongly supported the essential role of the avian ceca, present at the junction of the midgut and hindgut, in hindgut ENS development, since ablation of the cecal buds led to incomplete ENCDC colonization of the hindgut. In situ hybridization shows bone morphogenetic protein-4 (BMP4) is highly expressed in the cecal mesenchyme, leading us to hypothesize that cecal BMP4 is required for hindgut ENS development. To test this, we modulated BMP4 activity using embryonic intestinal organ culture techniques and retroviral infection. We show that overexpression or inhibition of BMP4 in the ceca disrupts hindgut ENS development, with GDNF playing an important regulatory role. Our results suggest that these two important signaling pathways are required for normal ENCDC migration and enteric ganglion formation in the developing hindgut ENS.

DOCK3-Associated Neurodevelopmental Disorder-Clinical Features and Molecular Basis.

The protein product of DOCK3 is highly expressed in neurons and has a role in cell adhesion and neuronal outgrowth through its interaction with the actin cytoskeleton and key cell signaling molecules. The DOCK3 protein is essential for normal cell growth and migration. Biallelic variants in DOCK3 associated with complete or partial loss of function of the gene were recently reported in six patients with intellectual disability and muscle hypotonia. Only one of the reported patients had congenital malformations outside of the CNS. Further studies are necessary to better determine the prevalence of DOCK3-associated neurodevelopmental disorders and the frequency of non-CNS clinical manifestations in these patients. Since deficiency of the DOCK3 protein product is now an established pathway of this neurodevelopmental condition, supplementing the deficient gene product using a gene therapy approach may be an efficient treatment strategy.

Negative pressure wound therapy promotes wound healing of diabetic foot ulcers by up-regulating PRDX2 in wound margin tissue

To understand the changes in the peroxiredoxin-2 (PRDX2) expression level in the wound margin tissue (T-PRDX2) of patients with diabetic foot ulcer (DFU) before and after negative pressure wound therapy (NPWT). Additionally, the study aimed to explore the association between PRDX2 expression and the treatment outcome of DFUs to provide a new theoretical basis for revealing the mechanism of NPWT promoting the healing of DFUs. Fifty-six type 2 diabetes patients with foot ulcers undergoing NPWT (the DFU group) and 28 patients with chronic lower limb skin ulcers with normal glucose tolerance undergoing NPWT (the skin ulcer control [SUC] group) were included in the study. T-PRDX2 was detected using Western blotting, and the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) and glutathione (GSH) levels were detected using a biochemical method. In addition, in vitro experiments were conducted to determine the effect of PRDX2 expression on normal human dermal fibroblast (NHDF) proliferation, migration, and apoptosis. Before NPWT, the DFU group exhibited a significantly lower T-PRDX2 expression level compared with the SUC group. After one week of NPWT, the T-PRDX2 expression level, SOD activity, and GSH content in the wound margin tissues of the DFU and SUC groups significantly increased compared with the before NPWT levels. Conversely, the inflammatory indicators (white blood cell, neutrophil percentage, C-reactive protein, and procalcitonin) and MDA content were significantly lower than the before NPWT levels. The expression changes of T-PRDX2 before and after NPWT in the DFU and SUC groups were positively correlated with the 4-week wound healing rate. In vitro experiments demonstrated that PRDX2 could alleviate the oxidative stress in NHDFs, thereby promoting their proliferation and migration, while reducing cell apoptosis. NPWT promotes DFU healing by increasing T-PRDX2, and changes in the T-PRDX2 might be associated with the therapeutic effect of NPWT.

Matrix Metalloproteinases and the Pathogenesis of Recurrent Corneal Erosions and Epithelial Basement Membrane Dystrophy.

Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes which are members of the zinc endopeptidase family. They have the ability to degrade extracellular matrix elements, allowing for the release of binding molecules and cell migration. Although metalloproteinases regulate numerous physiological processes within the cornea, overexpression of metalloproteinase genes and an imbalance between the levels of metalloproteinases and their inhibitors can contribute to the inhibition of repair processes, the development of inflammation and excessive cellular proliferation. The involvement of MMPs in the pathogenesis of dystrophic corneal diseases needs clarification. Our analyses focus on the involvement of individual metalloproteinases in the pathogenesis of recurrent corneal erosions and highlight their impact on the development of corneal epithelial basement membrane dystrophy (EBMD). We hypothesize that abnormalities observed in patients with EBMD may result from the accumulation and activation of metalloproteinases in the basal layers of the corneal epithelium, leading to basement membrane degradation. A barrier formed from degradation materials inhibits the normal migration of epithelial cells to the superficial layers, which contributes to the development of the aforementioned lesions. This hypothesis seems to be lent support by the elevated concentrations of metalloproteinases in the corneal epithelium of these patients found in our previous studies on the relationships between MMPs and recurrent corneal erosions.

GPR65 inhibits human trophoblast cell adhesion through upregulation of MYLK and downregulation of fibronectin via cAMP-ERK signaling in a low pH environment

BackgroundExtravillous trophoblasts (EVTs) are essential cells during the formation of the placenta, with the major function of invading the maternal decidua, anchoring the developing placenta to the uterus, remodeling uterine arteries, and regulating immune responses to prevent rejection. During early pregnancy, the decidua undergoes a hypoxic and acidic microenvironment, which has been shown to participate in tumor cell migration, invasion, growth, and angiogenesis. Nevertheless, the mechanisms by which EVTs sense and respond to the acidic microenvironment, thereby executing their functions, remain poorly understood.MethodsThe effects of G protein-coupled receptor 65 (GPR65) on cell adhesion and other cellular functions were tested using JAR spheroids, mouse blastocysts, and HTR-8/SVneo cells. Specifically, we employed HTR-8/SVneo cells for gene overexpression and silencing to investigate the underlying mechanism of GPR65's impact on trophoblast cell function under acidic conditions. Additionally, villus tissue samples obtained from early pregnancy loss patients were utilized to explore the potential association between GPR65 and its related signaling pathway molecules with the disease.ResultsThis study identified GPR65 expression widely in trophoblasts, with the highest level in EVTs. Importantly, optimal GPR65 levels are required for maintaining normal adhesion, migration, and invasion, whereas overexpression of GPR65 inhibits these functions by activating the cAMP-ERK signaling pathway, upregulating myosin light chain kinase (MYLK) and MYLK3 expression, and subsequently downregulating fibronectin. Consistently, elevated expression of GPR65, MYLK, and MYLK3 is observed in patients suffering from early pregnancy loss.ConclusionsThis work offers insights into the suppressive effects of GPR65 on EVT function under acidic conditions and highlights a putative target for therapeutic intervention in early pregnancy complications.E9R9tt1jd9fu3QritsNs7QVideo

Novel Long Non-Coding RNA (lncRNA) Transcript AL137782.1 Promotes the Migration of Normal Lung Epithelial Cells through Positively Regulating LMO7.

The role of long non-coding RNA (lncRNAs) in biological processes remains poorly understood, despite their significant impact. Our previous research discovered that the expression of AL137782.1, a long transcript of the novel lncRNA ENSG00000261553, is upregulated in lung epithelial cells upon exposure to microbes. Furthermore, the expression of AL137782.1 exhibits variability between para-cancerous and lung adenocarcinoma samples. These findings imply that this lncRNA may play a role in both normal lung epithelial cellular processes and pathophysiology. To elucidate the function of AL137782.1 in lung epithelial cells, we utilized bioinformatics retrieval and analysis to examine its expression. We then analyzed its subcellular localization using fluorescence in situ hybridization (FISH) and subcellular fractionation. Through rapid amplification of cDNA ends (RACE), we confirmed the presence of a 4401 nt lncRNA AL137782.1 in lung epithelial cells. Moreover, we discovered that this lncRNA positively regulates both mRNA and the protein expression of LMO7, a protein that may regulate the cell migration of normal lung epithelial cells. Although the overexpression of AL137782.1 has been shown to enhance the migration of both normal lung epithelial cells and lung adenocarcinoma cells in vitro, our study revealed that the expression of this lncRNA was significantly decreased in lung cancers compared to adjacent tissues. This suggests that the cell migration pattern regulated by the AL137782.1-LMO7 axis is more likely to occur in normal lung epithelial cells, rather than being a pathway that promotes lung cancer cell migration. Therefore, our study provides new insights into the mechanism underlying cell migration in human lung epithelial cells. This finding may offer a potential strategy to enhance normal lung epithelial cell migration after lung injury.

POU6F2 mutation in humans with pubertal failure alters GnRH transcript expression.

Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by the absence of pubertal development and subsequent impaired fertility often due to gonadotropin-releasing hormone (GnRH) deficits. Exome sequencing of two independent cohorts of IHH patients identified 12 rare missense variants in POU6F2 in 15 patients. POU6F2 encodes two distinct isoforms. In the adult mouse, expression of both isoform1 and isoform2 was detected in the brain, pituitary, and gonads. However, only isoform1 was detected in mouse primary GnRH cells and three immortalized GnRH cell lines, two mouse and one human. To date, the function of isoform2 has been verified as a transcription factor, while the function of isoform1 has been unknown. In the present report, bioinformatics and cell assays on a human-derived GnRH cell line reveal a novel function for isoform1, demonstrating it can act as a transcriptional regulator, decreasing GNRH1 expression. In addition, the impact of the two most prevalent POU6F2 variants, identified in five IHH patients, that were located at/or close to the DNA-binding domain was examined. Notably, one of these mutations prevented the repression of GnRH transcripts by isoform1. Normally, GnRH transcription increases as GnRH cells mature as they near migrate into the brain. Augmentation earlier during development can disrupt normal GnRH cell migration, consistent with some POU6F2 variants contributing to the IHH pathogenesis.

Movement behavior of swordfish provisions connectivity between the temperate and tropical southwest Pacific Ocean

Swordfish (Xiphias gladius) are a widely distributed (45°N–45°S) large pelagic fish targeted by fisheries worldwide. Swordfish that occur at high latitudes tend to disproportionately be large adults, so their movements have implications for population dynamics and fisheries management. In the southwest Pacific, little is known about this subset of the stock and existing evidence suggests limited movement from the subtropics into cooler high latitude waters. Here, we capitalize on the recent emergence of a recreational swordfish fishery off temperate southeast Australia to characterize movements of swordfish caught in the fishery with pop-up satellite archival transmitting tags. Data were recovered from tags deployed for 56–250 days on 11 swordfish (50–350 kg) tagged between 38 and 43°S in the western Tasman Sea. Five swordfish entered the Coral Sea (< 30°S), with four reaching north to 11–24°S, up to 3275 km away from location of capture. Behavior modelling suggests these four individuals rapidly transited north until encountering 23–27 °C water, at which point they lingered in the area for several months, consistent with spawning-related partial migration. One migrating swordfish still carrying a tag after the spawning season returned to ~ 120 km of its release location, suggesting site fidelity. Movements toward the central south Pacific were confined to two individuals crossing 165°E. Swordfish predominantly underwent normal diel vertical migration, descending into the mesopelagic zone at dawn (median daytime depth 494.9 m, 95% CI 460.4–529.5 m). Light attenuation predicted daytime depth, with swordfish rising by up to 195 m in turbid water. At night, swordfish were deeper during the full moon, median night-time depth 45.8 m (37.8–55.5) m versus 18.0 m (14.9–21.8) m at new moon. Modelling fine-scale (10 min−1) swordfish depth revealed dynamic effects of moon phase varying predictably across time of night with implications for fisheries interactions. Studying highly migratory fishes near distribution limits allows characterization of the full range of movement phenotypes within a population, a key consideration for important fish stocks in changing oceans.

HyperTP: A unified approach for live hypervisor replacement in datacenters

Maintenance of virtualized datacenters is often needed for the purposes of introducing new features, fixing bugs or mitigating security problems. However, current maintenance methods are either highly disruptive to the operation of VMs, utilize large amounts of computing resources or require high development efforts.We build HyperTP, a generic framework which combines in a unified way two approaches: in-place server micro-reboot-based hypervisor transplant (noted InPlaceTP) and live VM migration-based hypervisor transplant (noted MigrationTP). HyperTP hinges on a VM state hierarchy for organizing different types of hypervisor memory states in terms of their relation to VM execution, and an Unified Intermediate State Representation that abstracts VM-relevant memory states between multiple different hypervisors. We describe our implementations of both approaches, including technical details of our UISR design and the transplant process. Our evaluation results show that HyperTP delivers satisfactory performance: (1) MigrationTP changes a VM's underlying hypervisor while taking the same time and impacting virtual machines (VMs) with the same performance degradation as normal live migration; and (2) InPlaceTP imposes minimal VM downtime, even under increasing number of VMs and memory sizes. Finally, we discuss how the combination of InPlaceTP and MigrationTP can be used to address the challenges of upgrading a hypervisor cluster, and to mitigate known unpatched hypervisor vulnerabilities.

HnRNPL is essential for T cell function in the Periphery

Abstract While RNA binding proteins (RBPs) have recently emerged as regulators of gene expression in immune cells, their effect on T cell fate needs further investigation. Heterogeneous Nuclear Ribonucleoprotein (hnRNPs) are RBPs that play a crucial role in many aspects of RNA biogenesis, alternative splicing, expression, and function. During T cell development hnRNPL is known to regulate the proliferation, and migration of thymic pre-T cells, as loss of hnRNPL in early T cell development results in a failure of T cells to reach the periphery. Little is known about how hnRNPL affects T cell activation, and function. Our lab has used CD4 Cre × hnRNPL Fl/Fl(KO) mice to understand the role of hnRNPL in peripheral T cells. Our initial study of the steady state profile of the KO mice shows normal migration of T cells form the thymus, but there is a reduction in peripheral T cell numbers. We also show that hnRNPL plays an important role in T cell activation and survival, since T cells lacking hnRNPL do not survive long enough to differentiate into T helper cell subsets. In vivo, using immunization studies, we show that KO CD4 T cells fail to fully differentiate into Tfh and are unable to support the formation of germinal center B cells. To ensure the effect that hnRNPL has on T cells in the periphery is not caused by the loss of hnRNPL during thymic T cell development we are using the CD4-Cre/ERT2 × hnRNPL (I-KO) to investigate how the loss of hnRNPL in peripheral T cell affects the ability of T cells to differentiate and survive post activation. Further studies will also focus on the mechanisms hnRNPL use to regulate T cells activation and survival. These studies suggest that hnRNPL plays an important role in the activation and survival of peripheral T cells. AAI Fellowship

Fasciclin 2 plays multiple roles in promoting cell migration within the developing nervous system of Manduca sexta

The coordination of neuronal and glial migration is essential to the formation of most nervous systems, requiring a complex interplay of cell-intrinsic responses and intercellular guidance cues. During the development of the enteric nervous system (ENS) in Manduca sexta (tobacco hornworm), the IgCAM Fasciclin 2 (Fas2) serves several distinct functions to regulate these processes. As the ENS forms, a population of 300 neurons (EP cells) undergoes sequential phases of migration along well-defined muscle pathways on the visceral mesoderm to form a branching Enteric Plexus, closely followed by a trailing wave of proliferating glial cells that enwrap the neurons. Initially, both the neurons and glial cells express a GPI-linked form of Fas2 (GPI-Fas2), which helps maintain cell-cell contact among the pre-migratory neurons and later promotes glial ensheathment. The neurons then switch isoforms, predominantly expressing a combination of transmembrane isoforms lacking an intracellular PEST domain (TM-Fas2 PEST−), while their muscle band pathways on the midgut transiently express transmembrane isoforms containing this domain (TM-Fas2 PEST+). Using intracellular injection protocols to manipulate Fas2 expression in cultured embryos, we found that TM-Fas2 promotes the directed migration and outgrowth of individual neurons in the developing ENS. Concurrently, TM-Fas2 expression by the underlying muscle bands is also required as a substrate cue to support normal migration, while glial expression of GPI-Fas2 helps support their ensheathment of the migratory neurons. These results demonstrate how a specific IgCAM can play multiple roles that help coordinate neuronal and glial migration in the developing nervous system.

Naive songbirds show seasonally appropriate spring orientation in the laboratory despite having never completed first migration

The role of inherited orientation programmes in determining the outbound migratory routes of birds is increasingly well understood, though less is known about the influence of inherited information on return migration. Previous studies suggest that spatial gradient cues learnt through experience could be of considerable importance when relocating the natal site, though such cues could, in principle, augment rather than replace inherited migratory information. Here, we show that juvenile Eurasian blackcaps ( Sylvia atricapilla ) that have never left northwest Europe (i.e. never had the opportunity to learn navigational information on a continental scale) show significant spring orientation in a direction near-identical to that expected based on ringing recoveries from free-flying individuals. We suggest that this is probably indicative of birds inheriting an orientation programme for spring as well as autumn migration and speculate that, as long as the birds are not displaced far from their normal migration route, the use of inherited spring migratory trajectories might make uni-coordinate ‘stop signs’ sufficiently accurate for the long-distance targeting of their breeding sites.

Characterizing the role of Pdgfra in calvarial development.

Mammalian calvarium is composed of flat bones developed from two origins, neural crest, and mesoderm. Cells from both origins exhibit similar behavior but express distinct transcriptomes. It is intriguing to ask whether genes shared by both origins play similar or distinct roles in development. In the present study, we have examined the role of Pdgfra, which is expressed in both neural crest and mesoderm, in specific lineages during calvarial development. We found that in calvarial progenitor cells, Pdgfra is needed to maintain normal proliferation and migration of neural crest cells but only proliferation of mesoderm cells. Later in calvarial osteoblasts, we found that Pdgfra is necessary for both proliferation and differentiation of neural crest-derived cells, but not for differentiation of mesoderm-derived cells. We also examined the potential interaction between Pdgfra and other signaling pathway involved in calvarial osteoblasts but did not identify significant alteration of Wnt or Hh signaling activity in Pdgfra genetic models. Pdgfra is required for normal calvarial development in both neural crest cells and mesoderm cells, but these lineages exhibit distinct responses to alteration of Pdgfra activity.