The embryonic node functions as an instructive stem cell niche

In warm-blooded vertebrate embryos (mammals and birds), the body forms from a growth zone at the tail end. Hensen’s node, a region which induces and patterns the neural axis is located within this growth zone. The node also contains the precursors of neural, mesodermal and endodermal structures along the midline and has been suggested to contain a small population of resident stem cells. However, it is unknown whether the rest of the node constitutes an instructive stem cell niche, specifying stem cell behaviour. Here we combine transplantation of a single cell in vivo with single-cell mRNA sequencing in the chick and show that when made to enter the node, non-node-progenitor cells become resident and gain stem cell behaviour. These cells preferentially express G2/M phase cell-cycle related genes and are concentrated in posterior sub-regions of the node. The posterior part of the node therefore behaves as an instructive stem cell niche. These results demonstrate a new function for the vertebrate node during development

Development of ultrasound detection in American shad (Alosa sapidissima)

It has recently been shown that a few fish species, including American shad (Alosa sapidissima; Clupeiformes), are able to detect sound up to 180 kHz, an ability not found in most other fishes. Initially, it was proposed that ultrasound detection in shad involves the auditory bullae, swim bladder extensions found in all members of the Clupeiformes. However, while all clupeiformes have bullae, not all can detect ultrasound. Thus, the bullae alone are not sufficient to explain ultrasound detection. In this study, we used a developmental approach to determine when ultrasound detection begins and how the ability to detect ultrasound changes with ontogeny in American shad. We then compared changes in auditory function with morphological development to identify structures that are potentially responsible for ultrasound detection. We found that the auditory bullae and all three auditory end organs are present well before fish show ultrasound detection behaviourally and we suggest that an additional specialization in the utricle (one of the auditory end organs) forms coincident with the onset of ultrasound detection. We further show that this utricular specialization is found in two clupeiform species that can detect ultrasound but not in two clupeiform species not capable of ultrasound detection. Thus, it appears that ultrasound-detecting clupeiformes have undergone structural modification of the utricle that allows detection of ultrasonic stimulation

The nuclear lamina couples mechanical forces to cell fate in the preimplantation embryo via actin organization

During preimplantation development, contractile forces generated at the apical cortex segregate cells into inner and outer positions of the embryo, establishing the inner cell mass (ICM) and trophectoderm. To which extent these forces influence ICM-trophectoderm fate remains unresolved. Here, we found that the nuclear lamina is coupled to the cortex via an F-actin meshwork in mouse and human embryos. Actomyosin contractility increases during development, upregulating Lamin-A levels, but upon internalization cells lose their apical cortex and downregulate Lamin-A. Low Lamin-A shifts the localization of actin nucleators from nucleus to cytoplasm increasing cytoplasmic F-actin abundance. This results in stabilization of Amot, Yap phosphorylation and acquisition of ICM over trophectoderm fate. By contrast, in outer cells, Lamin-A levels increase with contractility. This prevents Yap phosphorylation enabling Cdx2 to specify the trophectoderm. Thus, forces transmitted to the nuclear lamina control actin organization to differentially regulate the factors specifying lineage identity

Solitary Esophageal Varix Simulating a Neoplasm

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73070/1/j.1440-1673.1988.tb02785.x.pd

The 894G>T variant in the endothelial nitric oxide synthase gene and spina bifida risk

The 894G>T single nucleotide polymorphism (SNP) in the endothelial NOS (NOS3) gene, has recently been associated with embryonic spina bifida risk. In this study, a possible association between the NOS3 894G>T SNP and spina bifida risk in both mothers and children in a Dutch population was examined using both a case-control design and a transmission disequilibrium test (TDT). Possible interactions between the NOS3 894G>T SNP and the MTHFR 677C>T SNP, elevated plasma homocysteine, and decreased plasma folate concentrations were also studied. The NOS3 894TT genotype did not increase spina bifida risk in mothers or children (OR 1.50, 95%CI 0.71–3.19 and OR 1.78, 95%CI 0.75–4.25, respectively). The TDT demonstrated no preferential transmission of the NOS3 894T allele (Χ2 = 0.06, P = 0.81). In combination with the MTHFR 677TT genotype or elevated plasma homocysteine concentrations, the NOS3 894GT/TT genotype increased maternal spina bifida risk (OR 4.52, 95%CI 1.55–13.22 and OR 3.38, 95%CI 1.46–7.84, respectively). In our study population, the NOS3 894GT/TT genotype might be a risk factor for having a spina bifida affected child in mothers who already have an impaired homocysteine metabolism

Developmental axon pruning mediated by BDNF-p75NTR–dependent axon degeneration

The mechanisms that regulate the pruning of mammalian axons are just now being elucidated. Here, we describe a mechanism by which, during developmental sympathetic axon competition, winning axons secrete brain-derived neurotrophic factor (BDNF) in an activity-dependent fashion, which binds to the p75 neurotrophin receptor (p75NTR) on losing axons to cause their degeneration and, ultimately, axon pruning. Specifically, we found that pruning of rat and mouse sympathetic axons that project to the eye requires both activity-dependent BDNF and p75NTR. p75NTR and BDNF are also essential for activity-dependent axon pruning in culture, where they mediate pruning by directly causing axon degeneration. p75NTR, which is enriched in losing axons, causes axonal degeneration by suppressing TrkA-mediated signaling that is essential for axonal maintenance. These data provide a mechanism that explains how active axons can eliminate less-active, competing axons during developmental pruning by directly promoting p75NTR-mediated axonal degeneration

Reasons for (Non)Participating in a Telephone-Based Intervention Program for Families with Overweight Children

Willingness to participate in obesity prevention programs is low; underlying reasons are poorly understood. We evaluated reasons for (non)participating in a novel telephone-based obesity prevention program for overweight children and their families. percentile) aged 3.5–17.4 years were screened via the CrescNet database, a representative cohort of German children, and program participation (repetitive computer aided telephone counseling) was offered by their local pediatrician. Identical questionnaires to collect baseline data on anthropometrics, lifestyle, eating habits, sociodemographic and psychosocial parameters were analyzed from 433 families (241 participants, 192 nonparticipants). Univariate analyses and binary logistic regression were used to identify factors associated with nonparticipation. percentile) was higher in participants (58.9% vs.38%,p<0.001). Participating girls were younger than boys (8.8 vs.10.4 years, p<0.001). 87.3% and 40% of participants, but only 72.2% and 24.7% of nonparticipants, respectively, reported to have regular breakfasts (p = 0.008) and 5 regular daily meals (p = 0.003). Nonparticipants had a lower household-net-income (p<0.001), but higher subjective physical wellbeing than participants (p = 0.018) and believed that changes in lifestyle can be made easily (p = 0.05).An important reason for nonparticipation was non-awareness of their child's weight status by parents. Nonparticipants, who were often low-income families, believed that they already perform a healthy lifestyle and had a higher subjective wellbeing. We hypothesize that even a low-threshold intervention program does not reach the families who really need it