Programmed cell death in type II neuroblast lineages is required for central complex development in the Drosophila brain

Background: The number of neurons generated by neural stem cells is dependent upon the regulation of cell proliferation and by programmed cell death. Recently, novel neural stem cells that amplify neural proliferation through intermediate neural progenitors, called type II neuroblasts, have been discovered, which are active during brain development in Drosophila. We investigated programmed cell death in the dorsomedial (DM) amplifying type II lineages that contribute neurons to the development of the central complex in Drosophila, using clonal mosaic analysis with a repressible cell marker (MARCM) and lineage-tracing techniques. Results: A significant number of the adult-specific neurons generated in these DM lineages were eliminated by programmed cell death. Programmed cell death occurred during both larval and pupal stages. During larval development, approximately one-quarter of the neuronal (but not glial) cells in the lineages were eliminated by apoptosis before the formation of synaptic connectivity during pupal stages. Lineage-tracing experiments documented the extensive contribution of intermediate neural progenitor-containing DM lineages to all of the major modular substructures of the adult central complex. Moreover, blockage of apoptotic cell death specifically in these lineages led to prominent innervation defects of DM-derived neural progeny in the major neuropile substructures of the adult central complex. Conclusions: Our findings indicate that significant neural overproliferation occurs normally in type II DM lineage development, and that elimination of excess neurons in these lineages through programmed cell death is required for the formation of correct neuropile innervation in the developing central complex. Thus, amplification of neuronal proliferation through intermediate progenitors and reduction of neuronal number through programmed cell death operate in concert in type II neural stem-cell lineages during brain development

The splicing co-factor Barricade/Tat-SF1, is required for cell cycle and lineage progression in Drosophila neural stem cells

Stem cells need to balance self-renewal and differentiation for correct tissue development and homeostasis. Defects in this balance can lead to developmental defects or tumor formation. In recent years, mRNA splicing has emerged as one important mechanism regulating cell fate decisions. Here we address the role of the evolutionary conserved splicing co-factor Barricade (Barc)/Tat-SF1/CUS2 in Drosophila neural stem cell (neuroblast) lineage formation. We show that Barc is required for the generation of neurons during Drosophila brain development by ensuring correct neural progenitor proliferation and differentiation. Barc associates with components of the U2 small nuclear ribonucleic proteins (snRNP), and its depletion causes alternative splicing in form of intron retention in a subset of genes. Using bioinformatics analysis and a cell culture based splicing assay, we found that Barc-dependent introns share three major traits: they are short, GC rich and have weak 3' splice sites. Our results show that Barc, together with the U2snRNP, plays an important role in regulating neural stem cell lineage progression during brain development and facilitates correct splicing of a subset of introns

Daily time-use patterns and obesity and mental health among primary school students in shanghai: a population-based cross-sectional study

Physical activity, screen viewing, sleep, and homework among children have been independently linked to health outcomes. However, few studies have assessed the independent associations between time spent in daily activities and children’s physical and mental health. This study describes time spent in four activities among primary school students in Shanghai, and examines the relationship between daily time-use patterns and obesity and mental health. The representative sample consists of 17,318 children aged 6–11 years in Shanghai. Time spent in moderate to vigorous physical activities (MVPA), screen viewing, sleep, and homework was measured by validated questionnaires. Logistic regressions were performed. We also fitted generalized additive models (GAM) and performed two-objective optimization to minimize the probability of poor mental health and obesity. In 2014, 33.7% of children spent ˂1 hour/day on MVPA, 15.6% spent ≥ 2 hours/day on screen viewing, 12.4% spent ˂ 9 hours/day on sleep, and 27.2% spent ≥ 2 hours/day on homework. The optimization results suggest that considering the 24-hour time limit, children face trade-offs when allocating time. A priority should be given to the duration of sleep and MVPA. Screen exposure should be minimized to save more time for sleep and other beneficial activities

Association between Dietary Patterns and Precocious Puberty in Children: A Population-Based Study

Objective. The aim of the present study was to investigate the association between dietary patterns and precocious puberty among Shanghai children. Methods. A cross-sectional study was conducted among Shanghai children by multistage stratified cluster random sampling in June 2014. Diet was assessed using a simplified food frequency questionnaire (FFQ). Height, weight, and Tanner stages of breast development, pubic hair growth, and testicular volume were carefully measured. Exploratory factor analysis was used to identify dietary patterns, and logistic regression analysis was used to assess the association between dietary patterns and precocious puberty. Results. Three distinct dietary patterns, “traditional diet,” “unhealthy diet,” and “protein diet,” were established. Neither the “traditional diet” pattern nor the “protein diet” pattern showed any association with precocious puberty, taking gender, BMI, and adjustment factors into consideration. The “unhealthy diet” pattern was significantly positively associated with precocious puberty in both boys (OR = 1.24, 95% CI = 1.02–1.51) and girls (OR = 1.31, 95% CI = 1.10–1.56). The relationship remained positive only for girls (OR = 1.25, 95% CI = 1.04–1.49) after adjustment for age and BMI but statistically nonsignificant after further adjustment for socioeconomic factors in both boys and girls. Conclusions. Dietary patterns were found to be related to precocious puberty among Shanghai children

The association between sleep and early pubertal development in Chinese children: a school population-based cross-sectional study

BackgroundThere is an increasing tendency toward early pubertal development, and sleep might be related to pubertal onset. We aimed to investigate the association of sleep duration and bedtime with early pubertal development.MethodsThis was a cross-sectional study of 8,007 children (53.6% boys) from Qufu city, Shandong province and Zhongshan city, Guangdong province, China. Data on sleep duration and bedtime were obtained by questionnaire. Early pubertal development was the primary outcome and it was evaluated by the pediatrician according to Tanner staging. Logistic regression models were used to separately examine the association between sleep duration or bedtime and early pubertal development, controlling body mass index (BMI), dietary pattern, soft drink, feeding pattern and mother’s BMI.ResultsIn boys, short sleep duration was strongly related to early pubertal development [OR (95%CI): 4.26 (1.30, 13.94)], and this association was intensified after adjusted BMI, dietary pattern, soft drink, feeding pattern and mother’s BMI. In girls, OR (95%CI) was 1.62 (1.04, 2.51), and increased after controlling BMI. Bedtime was associated with early pubertal development on weekdays [OR (95%CI): 6.39 (1.54, 26.45) in boys and 1.93 (1.23, 3.05) in girls], but not on weekends [OR (95%CI): 2.49 (0.61, 10.21) in boys; 1.31 (0.76, 2.25) in girls].ConclusionThis study underscores the positive association between the risk of early pubertal development and insufficient sleep duration and late bedtime

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Drosophila Neural Stem Cells in Brain Development and Tumor Formation

Neuroblasts, the neural stem cells in Drosophila, generate the complex neural structure of the central nervous system. Significant progress has been made in understanding the mechanisms regulating the self-renewal, proliferation, and differentiation in Drosophila neuroblast lineages. Deregulation of these mechanisms can lead to severe developmental defects and the formation of malignant brain tumors. Here, the authors review the molecular genetics of Drosophila neuroblasts and discuss some recent advances in stem cell and cancer biology using this model system

Targeted transgenic RNAi knockdown of cell fate determinants induces neoplastic tumor growth and metastasis in a Drosophila transplantation model of neural stem cell derived cancer

Genetic models such as Drosophila have sophisticated transgenic and molecular genetic tools available to investigate proliferation control in normal and tumorigenic neural stem cells. In this report, we adapted a targeted transgenic RNAi knockdown approach based on the Gal4/UAS expression system to the study of neoplastic tumor formation and metastatic growth in the Drosophila brain tissue transplantation model. Transgenic RNAi driven knockdown of numb, brain tumor (brat) and prospero (pros) in all neuroblasts (type I and type II) resulted in a high incidence of neoplastic tumor formation after transplantation that was comparable to that of loss-of-function mutations in these cell fate determinants. RNAi knockdown of numb and brat specifically restricted to type II neuroblast lineages also resulted in tumor formation after transplantation. A marked temperature dependence of tumor formation after transplantation was documented and quantified for RNAi-induced knockdown of numb, brat and pros. An in vivo assay for micrometastasis formation in ovarioles revealed significant metastatic potential of transplanted overproliferating brain tissue induced by RNAi knockdown of these cell fate determinants. These findings establish the foundation for RNAi-based investigations of the mechanisms which underlie the proliferation, invasion and metastastic potential of neural stem cell induced tumors in the Drosophila model

Novel cell lineages controlled by Pox neuro of larval poly-innervated external sensory organs in Drosophila

Previous studies have shown that Pox neuro (Poxn) plays a crucial role in the development of larval poly-innervated external sensory (p-es) organs in Drosophila. However, how Poxn exerts its function during these processes remains elusive. In this study, we described the detailed analysis of cell lineages for two larval p-es organs, kölbchen and papilla 6. Surprisingly, these two lineages are distinct from any cell lineage reported previously. In homozygous Poxn∆M22 mutant embryos, the kölbchen lineage gives rise to a reduced number of cells, and most interestingly, the cell division pattern is altered. Our results extend the understanding of the development of p-es organs in Drosophila larvae, and clearly demonstrate the role of Poxn in the specification of the cell lineages of larval p-es organs. Bisherige Untersuchungen haben gezeigt, dass Pox neuro (Poxn) eine wichtige Rolle in der Entwicklung larvaler poly-innervierter Sinnesorgane (p-es Organe) in Drosophila spielt. Aber wie Poxn diese Funktion ausübt, ist bis jetzt nicht klar bestimmt worden. In dieser Arbeit beschreiben wir die detaillierte Analyse von Zellstammbäumen für zwei larvale p-es Organe, das Kölbchen und die Papilla p6. Überraschenderweise sind die Zellteilungsmuster zur Bildung dieser Organe verschieden von allen bereits beschriebenen Zellstammbäumen. In Embryonen, die kein aktives Poxn Gen haben, verändert sich das Zellteilungsmuster der Kölbchenlinie und ihre Anzahl Zellen wird reduziert. Unsere Resultate erweitern die Erkenntnisse über die Entwicklung von p-es Organen und geben wichtige Hinweise über die Rolle von Poxn in der Spezifikation des Zellstammbaumes dieser larvalen, sensorischen Organe in Drosophila