Variety Of Developmental Pathways Research Articles

Role of autophagy and its significance in cellular homeostasis.

Autophagy is a catabolic pathway that regulates homeostasis in cells. It is an exceptional pathway of membrane trafficking. Autophagy is characterized by the formation of double-membrane vesicles; autophagosomes that are responsible for delivering damaged organelle and extra proteins to lysosome for recycling. A series of actions including environmental and genetic factors are responsible for induction of autophagy. In the past few decades, the research on autophagy has been immensely expanded because it is a vital process in maintaining cellular balance as well as deeply connected with pathogenesis of a number of diseases. The aim of this review is to present an overview of modern work on autophagy and highlight some essential genetic role in the induction of autophagy. There is an emerging need to identify, quantify, and manipulate the pathway of autophagy, due to its close relationship with a variety of developmental pathways and functions especially in cancer, diabetes, neurodegenerative disorders, and infectious diseases.

A genomewide survey of homeobox genes and identification of novel structure of the Hox cluster in the silkworm, Bombyx mori

Homeobox genes encode transcriptional factors that play crucial roles in a variety of developmental pathways from unicellular to multicellular eukaryotes. We have identified 102 homeobox genes in the typical insect of Lepidoptera, Bombyx mori, based on the newly assembled genome sequence with 9X coverage. These identified homeobox genes were categorized into nine classes including at least 74 families. The available ESTs and microarray data at present confirmed that more than half of them were expressed during silkworm developmental processes. Orthologs of pb, zen and ftz were newly identified in the Bombyx Hox cluster on chromosome 6. Interestingly, a special group of 12 tandemly duplicated homeobox genes was found located between Bmpb and Bmzen in the Bombyx Hox cluster, suggesting that Hox cluster might have experienced a lineage-specific expansion in the silkworm. A detailed analysis on genome data reveals that a split exists between Bmlab and Bmpb. Our data provide valuable information for future research on the development and evolution of silkworm.

Retinoic acid-inducible G protein-coupled receptors bind to frizzled receptors and may activate non-canonical Wnt signaling

Frizzled (Fz) seven-pass transmembrane receptors are Wnt receptors and function in a variety of developmental pathways. Here we identify retinoic acid-inducible gene-1, 2, 3, and 4 (RAIG1, 2, 3, and 4) as potential Fz binding proteins. RAIG proteins are seven-pass transmembrane receptors, and Xenopus RAIG2, 3, and 4 are expressed in early gastrula. XRAIG2 can activate small GTPases, such as RhoA, Rac, and Cdc42, and c-jun N-terminal kinase, thus exhibit activities that overlap with non-canonical Wnt/Fz signaling. Injection of XRAIG2 mRNA into Xenopus embryo causes a severe shortened and bent body axis due to defective gastrulation movements, reminiscent of abnormal non-canonical Wnt signaling. XRAIG2 affects convergent extension in activin-treated animal caps, which can be partially rescued by co-injection of a dominant-negative form of Cdc42. In zebrafish embryo, XRAIG2 also causes Ca 2+ flux, one of the consequences of non-canonical Wnt signaling. These results suggest a possible crosstalk/integration between Wnt/Frizzled and RAIG signal transduction pathways.

A Two-Step, PU.1-Dependent Mechanism for Developmentally Regulated Chromatin Remodeling and Transcription of the c-fms Gene

Hematopoietic stem cells and multipotent progenitors exhibit low-level transcription and partial chromatin reorganization of myeloid cell-specific genes including the c-fms (csf1R) locus. Expression of the c-fms gene is dependent on the Ets family transcription factor PU.1 and is upregulated during myeloid differentiation, enabling committed macrophage precursors to respond to colony-stimulating factor 1. To analyze molecular mechanisms underlying the transcriptional priming and developmental upregulation of the c-fms gene, we have utilized myeloid progenitors lacking the transcription factor PU.1. PU.1 can bind to sites in both the c-fms promoter and the c-fms intronic regulatory element (FIRE enhancer). Unlike wild-type progenitors, the PU.1(-/-) cells are unable to express c-fms or initiate macrophage differentiation. When PU.1 was reexpressed in mutant progenitors, the chromatin structure of the c-fms promoter was rapidly reorganized. In contrast, assembly of transcription factors at FIRE, acquisition of active histone marks, and high levels of c-fms transcription occurred with significantly slower kinetics. We demonstrate that the reason for this differential activation was that PU.1 was required to promote induction and binding of a secondary transcription factor, Egr-2, which is important for FIRE enhancer activity. These data suggest that the c-fms promoter is maintained in a primed state by PU.1 in progenitor cells and that at FIRE PU.1 functions with another transcription factor to direct full activation of the c-fms locus in differentiated myeloid cells. The two-step mechanism of developmental gene activation that we describe here may be utilized to regulate gene activity in a variety of developmental pathways.

The coherence of adolescent’s emotional and behavioral problems and changes over three years: Age and gender differences

Adolescent emotional and behavioural problems probably eventuate through a variety of developmental pathways and exposure to several risk factors. Several salient influences and concomitants associated with an increased risk of adolescent emotional and behavioural problems have been previously documented, including being female or male, low parental support, and substance use. The research focuses on adolescence as an important developmental period for understanding its emotional and behavioural problems and their correlations. To date, there have been few longitudinal studies on the possible structural relationships among emotional and behavioural problems in adolescent samples. The purpose of the present study was to gain a more comprehensive understanding of the longitudinal relationships among these factors and to demonstrate how they differ by sex. This study expands upon previous studies and upon the current body of literature by utilizing a longitudinal design and considering the stability and change of emotional and behavioural problems during adolescence. The longitudinal analyses contribute through clarifying ambiguities in previous findings of concurrent relations and longitudinal trends of emotional and behavioural problems. Finally, this investigation focused on a community sample, to enable a better generalization of the results to other community samples of troubled youth. Using a longitudinal sample, this study aims to analyze (1) how emotional and behavioural problems are associated with each other in adolescence, in different age groups, (2) how emotional and behavioural problems change over a three-year period, and (3) how these developmental tendencies are related to child’s gender. The sample consisted of 317 adolescents: 174 girls (55%) and 143 boys (45%). Emotional and behavioural problems were assessed at ages 14, 15 and 16 by the Youth Self Report (YSR) completed by the children. The study found that emotional and behavioural problems are associated: in all age groups, a coherence among anxiety/depression, somatic complaints, withdrawal, aggression and delinquency was apparent. Evidence suggests that emotional and behavioural problems, except withdrawal and delinquency, are relatively stable, however, the intensity of problems changes over time. Gender differences were apparent: in all age groups, girls scored higher than boys on anxiety/depression and somatic complaints, while boys scored higher than girls on the delinquency scale. The interactions between gender*age for anxiety/depression, somatic complaints, withdrawal, aggression and delinquency were not significant, implying that for both boys and girls these problems over a three-year period remained on the same level.

Phosphorylation of serine 239 of Groucho/TLE1 by protein kinase CK2 is important for inhibition of neuronal differentiation.

Transcriptional corepressors of the Groucho (Gro)/TLE family play important roles during a variety of developmental pathways, including neuronal differentiation. In particular, they act as negative regulators of neurogenesis, together with Hairy/Enhancer of split (Hes) DNA-binding proteins. The interaction with Hes1 leads to Gro/TLE hyperphosphorylation and increased transcription repression activity in mammalian cells, but the underlying molecular mechanisms are poorly characterized. We now show that Gro/TLE1 is phosphorylated in vivo by protein kinase CK2. This phosphorylation occurs at serine 239 within the conserved CcN domain present in all Gro/TLE family members. Mutation of serine 239 into alanine decreases Hes1-induced hyperphosphorylation of Gro/TLE1 and also reduces its nuclear association and transcription repression activity. We demonstrate further that Gro/TLE1 inhibits the transition of cortical neural progenitors into neurons and that its antineurogenic activity is inhibited by a serine-239-alanine mutation but not by a serine-239-glutamate mutation. These results suggest that CK2 phosphorylation of serine 239 of Gro/TLE1 is important for its function during neuronal differentiation.

Exhaustive identification of human class II basic helix–loop–helix proteins by virtual library screening

Cellular proliferation, specification and differentiation in developing tissues are tightly coordinated by groups of transcription factors in response to extrinsic and intrinsic signals. Furthermore, renewable pools of stem cells in adult tissues are subject to similar regulation. Basic helix–loop–helix (bHLH) proteins are a group of transcription factors that exert such a determinative influence on a variety of developmental pathways from C. elegans to humans, and we wished to exclusively identify novel members from within the whole human bHLH family. We have, therefore, developed an ‘empirical custom fingerprint’, to define the class II bHLH domain and exclusively identify these proteins in silico. We have identified nine previously uncharacterised human class II proteins, four of which were novel, by interrogating conceptual translations of the GenBank HTGS database. RT-PCR and mammalian 2-hybrid analysis of a subset of the factors demonstrated that they were indeed expressed, and were able to interact with an appropriate binding partner in vitro. Thus, we are now approaching an almost complete listing of human class II bHLH factors.

The differential diagnosis of impaired reciprocal social interaction in children: a review of disorders.

Impairment in reciprocal social interaction in children that is less severe than autism can be difficult to diagnose due to the variety of developmental pathways that may lead to this problem. Seven childhood disorders are reviewed that include impaired reciprocal interaction: multisystem developmental disorder, nonverbal learning disability syndrome, semantic-pragmatic disorder, attachment disorders (including a developmental theory of limbic system damage), multiplex developmental disorder, schizoid personality disorder, and pervasive developmental disorder not otherwise specified. Clarification is needed for most of the disorders in the areas of operationalized criteria, assessment tools, and documenting causal relationships.

The developmental pathways to schizophrenia: Potential moderating effects of stress

AbstractThe observations of family members as well as the results of past research suggest that a variety of developmental pathways can precede the onset of schizophrenia in early adulthood. In this article, we describe recent findings from our research on the childhood precursors of schizophrenia. Taken together, the results indicate that childhood behavioral, emotional, and motoric dysfunction occur at a higher rate in preschizophrenia subjects when compared to control subjects. Further, there are developmental changes as well as significant variability among schizophrenia patients in the nature and severity of childhood impairment. Drawing on the prevailing diathesis-stress model, we explore the moderating role that stress exposure and reactivity may play in the expression of the organic diathesis for schizophrenia. Specifically, we consider the role of the biological stress response in the production of developmental changes and individual differences in the pathways to schizophrenia. Given extant models of dopamine involvement in the neuropathology of schizophrenia, stress-induced Cortisol release may alter the expression of subcortical abnormalities in dopamine neurotransmission. Thus, we present a neural mechanism for the hypothesized behavioral sensitivity to stress exposure in schizophrenia, and explore the capacity of the model to account for the changing behavioral manifestations of vulnerability.

Syllepsis in Larixlaricina: analysis of tree leaders with and without sylleptic long shoots

Nonsylleptic and lightly, moderately, and heavily sylleptic leaders with 0 and 1–8, 9–17, and 18–38 sylleptic long shoots, respectively, were cut from 8-year-old Larixlaricina (Du Roi) K. Koch trees. The leaders showed considerable crookedness but degrees of crookedness were not significantly different among leader classes. Leaders of all classes bore sylleptic short shoots. These sylleptic short shoots were largest at midleader locations and larger on leaders with sylleptic long shoots than on nonsylleptic leaders. The terminal buds on many sylleptic short shoots were of long-shoot type. Some sylleptic short shoots with such buds occurred in mid- and proximal-leader positions, whereas lateral buds of the long-shoot type occurred only in distal-leader positions. Sylleptic long and short shoots greatly increased the numbers of leaves on the leaders. This leaf increase occurred principally on the proximal halves of the leaders where leader diameters also increased. Larger amounts of xylem accounted for most of the diameter increases. Subtending leaf to lateral axis distances increased acropetally among lateral buds and sylleptic shoots, but for the latter, these distances were greatest in the middle parts of the respective zones of occurrence. The large variety of developmental pathways for lateral axes on leaders was discussed.

The B-Chromosome System of Myrmeleotettix maculatus (Thunb). IV. The Dynamics

A necessary first step in the analysis oJ the population genetics of a given species is the adequate description, both in space and in time, of the genetic variation present in different populations of that species. Such variation may be studied in terms of two principal differences. First, allelic variation at individual loci, and second. variation in the structure and/or the number of chromosomes. Both, in fact, frequently lead to the development of polymorphic facies. Those associated with allelic variation are now relatively well understood for they have pronounced, often dramatic, effects on the exophenotype, effects which greatly facilitate an analysis of their adaptive roles. Thus allelic polymorphism is associated with mimicry in butterflies, with camouflage in moths and snails, with resistance to malarial parasites in man, and with floral biology in primroses (Sheppard, 1967). By contrast, most of the known chromosome polymorphisms are exophenotypically cryptic in character. It is often assumed that such polymorphisms are concerned, in some undefined way, with biochemical effects (see for example Wallace, 196,8), but the balance of evidence to date is that chromosome polymorphisms are expressed initially in the endophenotype rather than the exophenotype (John and Lewis, 1966). Coupled with this, the endophenotypic effects they promote can be either supplemented or counteracted by other components of the genetic system. Their study and their analysis is thus both more complex and more exacting than that of the conventional allelic nolvmornhisms. It comes as no surprise, therefore, to find that in very few instances have we any real appreciation of the factors which govern the presence or the frequency of particular chromosome polymorphisms in particular populations. British populations of the mottled or club-horned grasshopper, Myrmeleotettix maculatus, are polymorphic with respect to the presence of supernumerary or Bchromosomes (Barker, 1960; John and Hewitt, 1965a, b). These extra elements have no obvious immediate effect on exophenotype, as has been demonstrated by a study of five populations with from 10% to 40% B-chromosomes, in which five morphological characters were scored for each individual. The characters were (1) the number of stridulatory pegs per hind leg, (2) average length of tibiae (3) average length of femurs, (4) average length of wings, and (5) number of segments per antenna. These particular characters were chosen since they are important in a range of functions, from courtship and species recognition to movement and dispersal, and are probably influenced by a variety of developmental pathways. Table 1 contains a brief summary of the results from these five populations, all of which occur in a parkland about 3 miles across. There is no consistent picture with regard to differences between non-B and B-containing individuals within or between populations. The reason for considering the between-individual and within-individual variances, is because of the established effect of B-chromosomes on the chiasma frequency. Individuals with such supernumeraries have higher mean cell chiasma