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Human encephalization and developmental timing.

Human evolution is frequently analyzed in the light of changes in developmental timing. Encephalization in particular has been frequently linked to the slow pace of development in Homo sapiens. The "brain allometry extension" theory postulates that the progressive extension of a conserved primate brain allometry into postnatal life was the basis for brain enlargement in the human lineage. This study shows that published primate and human growth data do not corroborate this model. Instead, the unique encephalization of H. sapiens is alternatively described as the result of evolutionary changes in three aspects of developmental timing. The first is a moderate extension in the duration of brain growth relative to our closest extant relatives, contrary to the view that human brain growth is drastically prolonged into postnatal life. Second, humans evolved a derived brain allometry in comparison with chimpanzees and early hominins. Third, humans (and other anthropoid primates to a lesser degree) display a significant retardation in early postnatal body growth in comparison with other mammals, which directly affects adult encephalization in our species. The rejection of the "brain allometry extension" model may require a reevaluation of the adaptive scenarios proposed to explain how human encephalization evolved.

Animals↗

Developmental time course of acidic and basic fibroblast growth factors' expression in distinct cellular populations of the rat central nervous system.

Acidic and basic fibroblast growth factors (aFGF and bFGF, respectively) are expressed in high levels in adult central nervous system (CNS). We report the time course of developmental appearance and distribution of these factors and of two FGF receptors, FGFR-1 and FGFR-2, in the CNS of rats ranging in age from embryonic day 16 to adult. Immunohistochemical analysis showed that sensory neurons in the midbrain were the first cells to contain detectable aFGF immunoreactivity at embryonic day 18. The next cell group to contain aFGF were motor neurons, which were found to be aFGF-positive at the day of birth. A number of other subcortical neuronal populations were observed to contain aFGF immunoreactivity after postnatal day 7. Adult levels and distribution patterns of aFGF were reached in all CNS areas by postnatal day 28. Basic FGF immunoreactivity was observed at postnatal day 0 in neurons in the CA2 subfield of hippocampus. Astrocytes contained detectable bFGF immunoreactivity, starting at postnatal day 7. Adult levels and patterns of distribution of bFGF were reached in all CNS areas by postnatal day 28. These immunohistochemical observations were confirmed by using bioassay and Western blot techniques. FGFR-1 and FGFR-2 mRNA were expressed in significant levels in all CNS areas at all time points analyzed. The observation that aFGF and bFGF appear in specific and distinct cellular populations at relatively late developmental times suggests that these FGFs may be involved in specific mechanisms of CNS maturation, maintenance, and repair.

Animals↗

Expression and subcellular localization of the aryl hydrocarbon receptor nuclear translocator (ARNT) protein in mouse and chicken over developmental time.

The aryl hydrocarbon receptor nuclear translocator (ARNT) is a basic-helix-loop-helix/Per- ARNT-Sim (bHLH/PAS) transcription factor that is involved in multiple signaling pathways. This study focuses on the tissue distribution and subcellular localization of ARNT during embryological development of the mouse and chicken. Two different species were chosen to determine the consistency of the ARNT staining pattern. Immunohistochemical techniques were used to stain sections of embryos over three developmental time points for each species. Mouse tissues evaluated from embryonic day 10.5, 12.5, and 15, exhibited predominant nuclear staining with little change in expression patterns over time. Chicken tissues evaluated from embryonic day 2, 4, and 10 also showed predominant nuclear staining within all cells and little change in expression over developmental time, as well as, low levels of cytoplasmic ARNT staining in some cells. Importantly, in all tissues, the level of ARNT staining within the nuclear compartment was greater than staining observed in the cytoplasm. Thus, the overall conclusions from these studies are that i) the predominant subcellular localization of ARNT protein is nuclear, and ii) that mouse and chicken appear to maintain ARNT protein expression in many cell types over developmental time. These data support vertebrate ARNT as a nuclear transcription factor and a model in which dimerization partners require nuclear localization for interaction.

Animals↗

Dimensions of child maltreatment and children's adjustment: contributions of developmental timing and subtype.

This investigation examined the dimensions of developmental timing, subtype, and severity of maltreatment and their relations with child adaptation. The 814 children who participated in a summer day camp, 492 of whom were maltreated and 322 of whom were nonmaltreated comparison children, were assessed by camp counselors on their internalizing and externalizing symptomatology, aggressive, withdrawn, and cooperative behavior, and on personality dimensions of ego resiliency and ego control, and were rated by peers on disruptive, aggressive, and cooperative behavior. The severity within each subtype of maltreatment and the developmental period in which each subtype occurred were examined through hierarchical regression analyses. Additionally, children with similar timing or subtype patterns were grouped to explore diversity in outcomes. Results highlighted the role of severity of emotional maltreatment in the infancy-toddlerhood period and physical abuse during the preschool period in predicting externalizing behavior and aggression. Severity of physical neglect, particularly when it occurred during the preschool period, was associated with internalizing symptomatology and withdrawn behavior. Additionally, maltreatment during the school-age period contributed significant variance after earlier maltreatment was controlled. Chronic maltreatment, especially with onset during infancy-toddlerhood or preschool periods, was linked with more maladaptive outcomes. The implications of measuring multiple dimensions for improving research in child maltreatment are discussed.

Age Factors↗

The effect of chemically produced shifts in developmental timing on postmetamorphic morphology in Bombina orientalis.

The effect of altering developmental timing on postmetamorphic morphology was examined in the frog Bombina orientalis. The length of the larval period was manipulated with the use of a thyroid inhibitor. Results show that differences in time to metamorphosis are correlated with shifts in postmetamorphic relative hindlimb length. Furthermore, these differences in relative hindlimb length are similar to those found among closely related species. Variation in the timing of development may be responsible for a significant portion of the postmetamorphic shape variation found among frogs.

Animals↗

Dopamine D1 receptor changes due to caesarean section birth: effects of anesthesia, developmental time course, and functional consequences.

There is an epidemiological association between increased obstetric complications and disorders involving CNS dopamine dysregulation, such as schizophrenia. In light of this, a rat model of global hypoxia during Caesarean section (C-section) birth has been used to directly test if birth complications can produce long-term dopaminergic dysregulation. Previous studies have shown that, compared to vaginal birth, C-section birth alone (without additional global hypoxia) is sufficient to increase D1-like receptor binding in rat brain at adulthood. The current study examined (1) the developmental time course of changes in D1-like or D2-like receptors following C-section birth; (2) whether C-section birth from isoflurane-anesthetized dams also results in altered D1-like receptor levels, as does C-section from decapitated dams; and (3) behavioral responses to D1 and D2 agonists in rats born vaginally compared to C-section. Increases in nucleus accumbens D1-like receptor binding due to C-section birth were observed only at adulthood (3 months) but not prepubertally (1 month or 2 weeks). D2-like receptor binding levels were unaffected by C-section birth across the three developmental time points. Compared to vaginal birth, D1-like receptors were increased following C-section birth from isoflurane-anesthetized dams, as well as from decapitated dams. Adult rats that had been born by C-section showed enhanced D1 potentiation of D2-induced locomotor behavior. These studies indicate that C-section birth, from either anesthetized or unanesthetized dams, results in postpubertal increases in D1-like receptor binding and enhanced functional responses to D1 receptor activation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Developmental time courses of Na and Ca spikes in neuroblastoma X glioma hybrid cells.

The developmental time course of membrane excitability in neuroblastoma X glioma hybrid cells (NG108-15) was analyzed by measuring the electrical potential at each culture day after dBcAMP treatment. The maximum rate of rises of Na and Ca spikes which reflect their inward currents were measured in appropriate medium respectively. The Ca spike began to appear at 2-3 days in culture and reached its maximum on the fifth day. The Na spike began to appear at 3-4 days in culture and was completed on the seventh day. After then Ca and Na spikes remained constant and did not decrease even on the eighteenth day. Electrical excitability of the hybrid cells, as a whole, developed stepwise and was completed on the seventh day of culture.

Action Potentials↗

Multiple mechanisms are involved in regulating the expression of the developmental timing regulator lin-28 in Caenorhabditis elegans.

The timing of postembryonic developmental programs in Caenorhabditis elegans is regulated by a set of so-called heterochronic genes, including lin-28 that specifies second larval programs. lin-66 mutations described herein cause delays in vulval and seam cell differentiation, indicating a role for lin-66 in timing regulation. A mutation in daf-12/nuclear receptor or alg-1/argonaute dramatically enhances the retarded phenotypes of the lin-66 mutants, and these phenotypes are suppressed by a lin-28 null allele. We further show that the LIN-28 protein level is upregulated in the lin-66 mutants and that this regulation is mediated by the 3'UTR of lin-28. We have also identified a potential daf-12-response element within lin-28 3'UTR and show that two microRNA (miRNA) (lin-4 and let-7)-binding sites mediate redundant inhibitory activities that are likely lin-66-independent. Quantitative PCR data suggest that the lin-28 mRNA level is affected by lin-14 and miRNA regulation, but not by daf-12 and lin-66 regulation. These results suggest that lin-28 expression is regulated by multiple independent mechanisms including LIN-14-mediated upregulation of mRNA level, miRNAs-mediated RNA degradation, LIN-66-mediated translational inhibition and DAF-12-involved translation promotion.

3' Untranslated Regions↗

The C. elegans heterochronic gene lin-46 affects developmental timing at two larval stages and encodes a relative of the scaffolding protein gephyrin.

The succession of developmental events in the C. elegans larva is governed by the heterochronic genes. When mutated, these genes cause either precocious or retarded developmental phenotypes, in which stage-specific patterns of cell division and differentiation are either skipped or reiterated, respectively. We identified a new heterochronic gene, lin-46, from mutations that suppress the precocious phenotypes caused by mutations in the heterochronic genes lin-14 and lin-28. lin-46 mutants on their own display retarded phenotypes in which cell division patterns are reiterated and differentiation is prevented in certain cell lineages. Our analysis indicates that lin-46 acts at a step immediately downstream of lin-28, affecting both the regulation of the heterochronic gene pathway and execution of stage-specific developmental events at two stages: the third larval stage and adult. We also show that lin-46 is required prior to the third stage for normal adult cell fates, suggesting that it acts once to control fates at both stages, and that it affects adult fates through the let-7 branch of the heterochronic pathway. Interestingly, lin-46 encodes a protein homologous to MoeA of bacteria and the C-terminal domain of mammalian gephyrin, a multifunctional scaffolding protein. Our findings suggest that the LIN-46 protein acts as a scaffold for a multiprotein assembly that controls developmental timing, and expand the known roles of gephyrin-related proteins to development.

Adaptor Proteins, Signal Transducing↗

Developmental time and mortality of the reduviid bug Triatoma infestans with differential exposure to coprophagic infections with Blastocrithidia triatomae (Trypanosomatidae).

Developmental time and survival in larvae of the reduviid bug Triatoma infestans were studied in uninfected groups and in those exposed to a coprophagic infection with Blastocrithidia triatomae. Addition to young uninfected larvae of (a) different numbers of infected bugs, (b) infected and uninfected bugs, and (c) fresh or dry infectious feces were compared. Retardation of development was evident in groups given infected larvae or fresh feces. Mortality rates were correlated with infection rates and were higher in groups given more infected bugs, independent of the presence of uninfected bugs. Therefore, bugs did not discriminate between feces from infected and uninfected bugs, or they did not reject infectious feces. Dry feces had to be redissolved with fresh feces before infection was possible.

Animals↗

Duration and developmental timing of poverty and children's cognitive and social development from birth through third grade.

Relations of duration and developmental timing of poverty to children's development from birth to age 9 were examined by comparing children from families who were never poor, poor only during the child's infancy (0-3 years of age), poor only after infancy (4-9 years of age), and chronically poor. Chronically poor families provided lower quality childrearing environments, and children in these families showed lower cognitive performance and more behavior problems than did other children. Any experience of poverty was associated with less favorable family situations and child outcomes than never being poor. Being poor later tended to be more detrimental than early poverty. Mediational analyses indicated that poverty was linked to child outcomes in part through less positive parenting.

Child↗

Longevity differences among lines artificially selected for developmental time and wing length in Drosophila buzzatii.

We assessed the indirect response of longevity in lines selected for wing length (WL) and developmental time (DT). Longevity in selection lines was compared to laboratory control lines and the offspring of recently collected females. Wild flies (W lines), flies from lines selected for fast development (F lines), and for fast development and large wing length (L lines) outlived control laboratory lines (C lines) and lines selected for fast development and short wing (S lines). The decline in longevity in S lines is in line with the idea that body size and longevity are correlated and may be the result of the fixation of alleles at loci affecting pleiotropically the two traits under selection and longevity. In addition, inbreeding and artificial selection affected the correlation between wing length and longevity that occurs in natural populations of Drosophila buzzatii, suggesting that correlations between traits are not a perdurable feature in a population.

Aging↗

Developmental timing in C. elegans is regulated by kin-20 and tim-1, homologs of core circadian clock genes.

In Caenorhabditis elegans, heterochronic genes constitute a developmental timer that specifies temporal cell fate selection. The heterochronic gene lin-42 is the C. elegans homolog of Drosophila and mammalian period, key regulators of circadian rhythms, which specify changes in behavior and physiology over a 24 hr day/night cycle. We show a role for two other circadian gene homologs, tim-1 and kin-20, in the developmental timer. Along with lin-42, tim-1 and kin-20, the C. elegans homologs of the Drosophila circadian clock genes timeless and doubletime, respectively, are required to maintain late-larval identity and prevent premature expression of adult cell fates. The molecular parallels between circadian and developmental timing pathways suggest the existence of a conserved molecular mechanism that may be used for different types of biological timing.

Animals↗

Physeal replacement with cultured chondrocytes of varying developmental time: failure to reconstruct a functional or structural physis.

Reconstruction of physeal regions excised from the distal femoral chondroepiphysis was attempted in a murine model. Cultured chondrocytes of varying developmental time from the same inbred strain of mice were used for replacement. Vascularity, matrix formation, and cell division, as well as growth, were assessed. The cultured chondrocytes did not produce growth. Consistent with this, cell division, as assessed with incorporation of tritiated thymidine, was not normal. However, the cultured chondrocytes did receive a nutritional supply from the host and did continue matrix formation after transplantation.

Animals↗

Regulatory mutations of mir-48, a C. elegans let-7 family MicroRNA, cause developmental timing defects.

The C. elegans heterochronic genes program stage-specific temporal identities in multiple tissues during larval development. These genes include the first two miRNA-encoding genes discovered, lin-4 and let-7. We show that lin-58 alleles, identified as lin-4 suppressors, define another miRNA that controls developmental time. These alleles are unique in that they contain point mutations in a gene regulatory element of mir-48, a let-7 family member. mir-48 is expressed prematurely in lin-58 mutants, whereas expression of mir-241, another let-7 family member residing immediately upstream of mir-48, appears to be unaffected. A mir-48 transgene bearing a lin-58 point mutation causes strong precocious phenotypes in the hypodermis and vulva when expressed from multicopy arrays. mir-48::gfp fusions reveal expression in these tissues, and inclusion of a lin-58 mutation causes precocious and enhanced gfp expression. These results suggest that lin-58 alleles disrupt a repressor binding site that restricts the time of miR-48 action in wild-type animals.

Animals↗

Effect of larval diet on cat flea (Siphonaptera: Pulicidae) developmental times and adult emergence.

The natural diet of cat flea, Ctenocephalides felis (Bouche), larvae is primarily adult flea feces, but dried bovine blood may be substituted in the laboratory. Percentage adult emergence (79.4% on feces; 78.9% on blood) and developmental times (20.6 d on feces; 17.1 d on blood) did not significantly differ for the two diets. The drying temperature of blood determined its quality; blood dried at 120 degrees C was unsatisfactory for larval development. The dietary value of dried bovine blood was not enhanced when supplemented with brewer's yeast, rodent chow, or a combination of those constituents. Blood particle size ranging from less than 180 to greater than 500u did not affect the value of blood as a diet. Rodent chow, yeast, albumen, hemoglobin, and mixtures of these constituents were unsuitable as larval diets.

Animals↗

Influence of sex, developmental time and food on beta-N-acetylglucosaminidase activity in the rice weevil Sitophilus oryzae L.

The effects of some biological parameters on beta-N-acetylglucosaminidase activity have been investigated in S. oryzae. There is no significant influence of sex and developmental time on the enzyme activity level, which appears in contrast to be greatly influenced by food (wheat or sorghum). Sorghum contains competitive inhibitors which are almost completely removed after dialysis. Fasting relieves this inhibition very quickly, suggesting that inhibitors act directly at the gut level.

Acetylglucosaminidase↗

Changes in gravitational force affect gene expression in developing organ systems at different developmental times.

BACKGROUND: Little is known about the affect of microgravity on gene expression, particularly in vivo during embryonic development. Using transgenic zebrafish that express the gfp gene under the influence of a beta-actin promoter, we examined the affect of simulated-microgravity on GFP expression in the heart, notochord, eye, somites, and rohon beard neurons. We exposed transgenic zebrafish to simulated-microgravity for different durations at a variety of developmental times in an attempt to determine periods of susceptibility for the different developing organ systems. RESULTS: The developing heart had a period of maximum susceptibility between 32 and 56 hours after fertilization when there was an approximately 30% increase in gene expression. The notochord, eye, somites, and rohon beard neurons all showed periods of susceptibility occurring between 24 and 72 hours after fertilization. In addition, the notochord showed a second period of susceptibility between 8 and 32 hours after fertilization. Interestingly, all organs appeared to be recovering by 80 hours after fertilization despite continued exposure to simulated-microgravity. CONCLUSION: These results support the idea that exposure to microgravity can cause changes in gene expression in a variety of developing organ systems in live embryos and that there are periods of maximum susceptibility to the effects.

Animals↗