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Biomedical subjects

W A Harris

Publications and source records attributed to W A Harris.

At least 55 records · Page 3Linked to original sources
PubMed1997

Xath5 participates in a network of bHLH genes in the developing Xenopus retina.

We examined the function of basic-helix-loop-helix (bHLH) transcription factors during retinal neurogenesis. We identified Xath5, a Xenopus bHLH gene related to Drosophila atonal, which is expressed in the developing Xenopus retina. Targeted expression of Xath5 in retinal progenitor cells biased the differentiation of these cells toward a ganglion cell fate, suggesting that Xath5 can regulate the differentiation of retinal neurons. We examined the relationship between the three bHLH genes Xash3, NeuroD, and Xath5 during retinal neurogenesis and found that Xash3 is expressed in early retinoblasts, followed by coexpression of Xath5 and NeuroD in differentiating cells. We provide evidence that the expression of Xash3, NeuroD, and Xath5 is coupled and propose that these bHLH genes regulate successive stages of neuronal differentiation in the developing retina.

Aging↗
PubMed1997

Cellular diversification in the vertebrate retina.

The discovery of heterogeneous populations of retinal precursors with sequentially modified fates may help solve the conundrum of conserved histogenesis in the absence of determination either by birthdate or lineage. Combined with a wealth of new data on the exogenous and endogenous factors that influence cellular fate in the retina, models of how complexity is generated are beginning to emerge.

Animals↗
PubMed1997

Xenopus Pax-6 and retinal development.

We have cloned a homolog of Pax-6 in Xenopus laevis. Its deduced amino acid sequence has a 95% overall identity with Pax-6 homologs in other vertebrates. It is expressed early in development in cells fated to form the eye and parts of the forebrain, hindbrain, and spinal cord. It has two phases of expression in the eye. In the early phase, from stage 12.5 to stage 33/34, Xenopus Pax-6 is expressed throughout the developing retina. In the late phase, after stage 33/34, it is excluded from mature cells in the outer half of the retina and from cells in the ciliary marginal zone, remaining only in amacrine and ganglion cells. Misexpression of Pax-6 early in development results in axial defects, but no specific eye phenotype is observed. Targeted misexpression in the retina at later stages does not result in any significant bias toward formation of amacrine or ganglion cells or away from photoreceptors. Ectopic expression of the proneural gene NeuroD alters the pattern of Pax-6, substantially reducing its expression in the eye field and later reducing or eliminating the eye itself. Our results show that Pax-6 expression appears to be necessary, but not sufficient, for eye formation in Xenopus.

Amino Acid Sequence↗
PubMed1997

Xenopus Brn-3.0, a POU-domain gene expressed in the developing retina and tectum. Not regulated by innervation.

PURPOSE: To study the effect of denervation on the expression of the POU-domain gene Brn-3.0 in the Xenopus visual system. METHODS: An oligonucleotide probe was used to identify homologs of the murine gene Brn-3.0 in the retina. In situ hybridization was used to determine the spatial distribution of the mRNA within the developing embryo. To study the effects of denervation on Brn-3.0 expression and cell fate, embryonic eyes were transplanted to an ectopic location on the animal (the flank) before the onset of retinal ganglion cell (RGC) axonogenesis. Gene expression in ectopic eyes and denervated tecta was analyzed over time using in situ hybridization. RESULTS: The deduced, partial amino acid sequence for Xenopus Brn-3.0 shows 100% identity with the mouse Brn-3.0 and the human Brn-3a gene products. It is expressed during early embryonic development in distinct populations of the neural crest and later in specific cranial ganglia. It also is expressed in RGCs and in the optic tectum, beginning before the first RGC axons have reached the tectum and continuing without interruption throughout the period when retino-tectal connections are established and refined. If the retino-tectal projection is kept from forming by transplanting one eye to an ectopic location, Brn-3.0 expression is unaffected in both the ectopic eye and the denervated side of the tectum. CONCLUSIONS: Coordinate expression of Brn-3.0 in afferent and efferent pathways suggests mutual regulation. However, the authors' evidence shows that expression in the retina is not regulated by target-derived factors nor is expression in the tectum regulated by retinal innervation.

Animals↗
PubMed1996

Youth Risk Behavior Surveillance--United States, 1995.

PROBLEM/CONDITION: Priority health-risk behaviors that contribute to the leading causes of mortality, morbidity, and social problems among youth and adults often are established during youth, extend into adulthood, and are interrelated. REPORTING PERIOD: February through May 1995. DESCRIPTION OF THE SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries, tobacco use, alcohol and other drug use, sexual behaviors, unhealthy dietary behaviors, and physical inactivity. The YRBSS includes both a national school-based survey conducted by CDC and state and local school-based surveys conducted by state and local education agencies. This report summarizes results from the national survey, 35 state surveys, and 16 local surveys conducted among high school students from February through May 1995. RESULTS AND INTERPRETATION: In the United States, 72% of all deaths among school-age youth and young adults result from four causes: motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1995 YRBSS suggest that many high school students practice behaviors that may increase their likelihood of death from these four causes: 21.7% had rarely or never used a safety belt, 38.8% had ridden with a driver who had been drinking alcohol during the 30 days preceding the survey, 20.0% had carried a weapon during the 30 days preceding the survey, 51.6% had drunk alcohol during the 30 days preceding the survey, 25.3% had used marijuana during the 30 days preceding the survey, and 8.7% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among school-age youth and young adults also result from unintended pregnancies and sexually transmitted diseases, including human immunodeficiency virus infection. YRBSS results indicate that in 1995, 53.1% of high school students had had sexual intercourse, 45.6% of sexually active students had not used a condom at last sexual intercourse, and 2.0% had ever injected an illegal drug. Among adults, 65% of all deaths result from three causes: heart disease, cancer and stroke. Most of the risk behaviors associated with these causes of death are initiated during adolescence. In 1995, 34.8% of high school students had smoked cigarettes during the 30 days preceding the survey, 39.5% had eaten more than two servings of foods typically high in fat content during the day preceding the survey, and only 25.4% had attended physical education class daily. ACTIONS TAKEN: YRBSS data are being used nationwide by health and education officials to improve national, state, and local policies and programs designed to reduce risks associated with the leading causes of mortality and morbidity. YRBSS data also are being used to measure progress toward achieving 21 national health objectives and one of eight National Education Goals.

Accidents↗
PubMed1996

Engrailed and retinotectal topography.

We examine the role of the Engrailed homeobox gene in establishment of local tectal topography. In the mesencephalon, a gradient of Engrailed appears early and defines the rostrocaudal axis of the tectum. Various experiments that cause ectopic Engrailed expression cause predictable readjustments of the retinotectal map. The newly discovered 'realisators' of the retinotopic map, such as receptor tyrosine kinase ligands ELF-1 and RAGS could be controlled directly by Engrailed. Indeed, recent results show that Engrailed regulates the expression of these ligands. The Engrailed gradient itself appears to be set up by signals including FGF8 and WNTI, allowing us to begin to trace the molecular cascade that is responsible for the correct wiring of the visual projection back into the early embryo.

Animals↗
PubMed1996

Engrailed, retinotectal targeting, and axonal patterning in the midbrain during Xenopus development: an antisense study.

Axonal tracts in the vertebrate brain seem to respect domains of homeobox gene expression. To test the role of engrailed in tract formation in the midbrain, we inhibited its expression using antisense (AS) oligonucleotides. Phosphorothioate-modified AS oligos caused navigational errors in both the optic projection (OP) and the intertectal commissure (ITC). These oligos, however, also inhibited bFGF binding to the brain. To determine whether these tract phenotypes were due to inhibition of bFGF function or engrailed expression, we used partially phosphorothioate-modified (pp) oligos, which inhibit engrailed expression but do not affect bFGF binding. These ppAS oligos caused the ITC phenotype but had no effect on the OP. Thus, interference with bFGF function correlates with the OP phenotype, while the ITC phenotype is directly related to engrailed expression.

Animals↗
PubMed1996

Youth risk behavior surveillance--United States, 1995.

Priority health-risk behaviors that contribute to the leading causes of mortality, morbidity, and social problems among youth and adults often are established during youth, extend into adulthood, and are interrelated. The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries, tobacco use, alcohol and other drug use, sexual behaviors, unhealthy dietary behaviors, and physical inactivity. The YRBSS includes both a national school-based survey conducted by CDC and state and local school-based surveys conducted by state and local education agencies. This report summarizes results from the national survey, 35 state surveys, and 16 local surveys conducted among high school students from February through May 1995. In the United States, 72% of all deaths among school-age youth and young adults result from four causes: motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1995 YRBSS suggest that many high school students practice behaviors that may increase their likelihood of death from these four causes: 21.7% had rarely or never used a safety belt, 38.8% had ridden with a driver who had been drinking alcohol during the 30 days preceding the survey, 20.0% had carried a weapon during the 30 days preceding the survey, 51.6% had drunk alcohol during the 30 days preceding the survey, 25.3% had used marijuana during the 30 days preceding the survey, and 8.7% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among school-age youth and young adults also result from unintended pregnancies and sexually transmitted diseases, including HIV infection. YRBSS results indicate that in 1995, 53.1% of high school students had experienced sexual intercourse, 45.6% of sexually active students had not used a condom at last sexual intercourse, and 2.0% had ever injected an illegal drug. Among adults, 65% of all deaths result from three causes: heart disease, cancer, and stroke. Most of the risk behaviors associated with these causes of death are initiated during adolescence. In 1995, 34.8% of high school students had smoked cigarettes during the 30 days preceding the survey, 39.5% had eaten more than two servings of foods typically high in fat content during the day preceding the survey, and only 25.4% had attended physical education class daily. YRBSS data are being used nationwide by health and education officials to improve national, state, and local policies and programs designed to reduce risks associated with the leading causes of mortality and morbidity. YRBSS data also are being used to measure progress toward achieving 21 national health objectives and one of eight National Education Goals.

Adolescent↗
PubMed1996

Signal transduction in vertebrate growth cones navigating in vivo.

Navigating growth cones need signal transduction machinery to amplify and transmit the effects of extracellular signals throughout the growth cone. In culture, many drugs that affect second messengers are known to modulate neurite extension (with different effects on different neurons), and gradients of calcium influx and cyclic nucleotide analogs can cause growth cones to turn. However, it is not clear which of these responses are physiologically relevant, as axons grow through much more complex environments in vivo. The "exposed brain" preparation in Xenopus embryos provides an experimentally tractable system in which it is possible to study growth, pathfinding, and target recognition of retinal growth cones in vivo, while pharmacologically manipulating their signal transduction systems. These growth cones can also be easily studied in explant culture. We describe preliminary results of parallel in vivo and in vitro experiments using an array of drugs that perturb transduction molecules. Surprisingly, calcium ionophores and cyclic nucleotide analogs have no significant effect on retinal axon growth or pathfinding. Several agents including herbimycin A, ML-7, mastoparan, and RHC80267 inhibit retinal axon growth, both in vivo and in vitro, suggesting that tyrosine kinases, myosin, heterotrimeric G-proteins, and diacylglycerol lipase are important for retinal growth cones navigating in the optic pathway.

Animals↗
PubMed1995

Youth risk behavior surveillance--United States, 1993.

PROBLEM/CONDITION: Priority health risk behaviors that contribute to the leading causes of mortality, morbidity, and social problems among youth and adults often are established during youth, extend into adulthood, and are interrelated. REPORTING PERIOD: February through May 1993. DESCRIPTION OF SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries, tobacco use, alcohol and other drug use, sexual behaviors, dietary behaviors, and physical activity. The YRBSS includes a national, school-based survey conducted by CDC and state and local school-based surveys conducted by state and local education agencies. This report summarizes results from the national survey, 24 state surveys, and nine local surveys conducted among high school students during February through May 1993. RESULTS AND INTERPRETATION: In the United States, 72% of all deaths among school-age youth and young adults are from four causes: motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1993 YRBSS suggest that many high school students practice behaviors that may increase their likelihood of death from these four causes: 19.1% rarely or never used a safety belt, 35.3% had ridden with a driver who had been drinking alcohol during the 30 days preceding the survey, 22.1% had carried a weapon during the 30 days preceding the survey, 80.9% ever drank alcohol, 32.8% ever used marijuana, and 8.6% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among adolescents also result from unintended pregnancies and sexually transmitted diseases, including human immunodeficiency virus (HIV) infection. YRBSS results indicate that in 1993, 53.0% of high school students had had sexual intercourse, 52.8% of sexually active students had used a condom during last sexual intercourse, and 1.4% ever injected an illegal drug. Among adults, 67% of all deaths are from three causes: heart disease, cancer, and stroke. In 1993, many high school students practiced behaviors that may increase the risk for these health problems: 30.5% of high school students had smoked cigarettes during the 30 days preceding the survey, only 15.4% had eaten five or more servings of fruits and vegetables during the day preceding the survey, and only 34.3% had attended physical education class daily. ACTIONS TAKEN: YRBSS data are being used nationwide by health and education officials to improve school health policies and programs designed to reduce risks associated with the leading causes of mortality and morbidity. At the national level, YRBSS data are being used to measure progress toward achieving 26 national health objectives and one of eight National Education Goals.

Accidents↗
PubMed1995

Fate of the anterior neural ridge and the morphogenesis of the Xenopus forebrain.

The fate of the anterior neural ridge was studied by following the relative movements of simultaneous spot applications of DiI and DiO from stage 15 through stage 45. These dye movements were mapped onto the neuroepithelium of the developing brain whose shape was gleaned from whole-mount in situs to neural cell adhesion molecule and dissections of the developing nervous system. The result is a model of the cell movements that drive the morphogenesis of the forebrain. The midanterior ridge moves inside and drops down along the most anterior wall of the neural tube. It then pushes forward a bit, rotates ventrally during forebrain flexing, and gives rise to the chiasmatic ridge and anterior hypothalamus. The midanterior plate drops, forming the floor of the forebrain ventricle, and, keeping its place behind the ridge, it gives rise to the posterior hypothalamus or infundibulum. The midlateral anterior ridge slides into the lateral anterior wall of the neural tube and stretches laterally into the optic stalk and retina, and then rotates into a ventral position. The lateral anterior ridge converges to the most anterior part of the dorsal midline during neural tube closure, then rotates anteriorly, and gives rise to telencephalic structures. Whole-mount bromodeoxyuridine labeling at these stages showed that cell division is widespread and relatively uniform throughout the brain during the late neurula and early tailbud stages, but that during late tailbud stages cell division becomes restricted to specific proliferative zones. We conclude that the early morphogenesis of the brain is carried out largely by choreographed cell movements and that later morphogenesis depends on spatially restricted patterns of cell division.

Animals↗
PubMed1995

A Drosophila E(spł) gene is "neurogenic" in Xenopus: a green fluorescent protein study.

A Drosophila Enhancer of split [E(spl)] bHLH protein, m delta, was misexpressed in Xenopus embryos along with green fluorescent protein (GFP) as a lineage label. The Drosophila protein translocated to the nucleus of Xenopus cells and led to neural hypertrophy in the GFP-labeled dorsal ectoderm, a phenotype similar to that caused by the misexpression of activated Xotch. Our data indicate a strong conservation in E(spl)bHLH function in the Notch signaling pathway of flies and vertebrates.

Animals↗
PubMed1995

Xotch inhibits cell differentiation in the Xenopus retina.

The neurogenic gene Xotch acts to divert cellular determination during gastrulation in Xenopus embryos. We examined the role of Xotch in the developing retina, where cell signaling events are thought to affect differentiation. Xotch is expressed in undifferentiated precursor cells of the ciliary marginal zone and late embryonic central retina. It is not expressed in stem cells or in differentiated neurons and glia. Expression in the retina is spatially restricted even in the absence of cell division. The final Xotch-positive precursor cells in the central retina mostly differentiate as Müller glia, suggesting that this is the last available fate of cells in the frog retina. Transfection of an activated form of Xotch into isolated retinal cells causes them to retain a neuroepithelial morphology, indicating that the continued activation of Xotch inhibits cell differentiation.

Aging↗
PubMed1995

Youth risk behavior surveillance--United States, 1993.

Priority health risk behaviors that contribute to the leading causes of mortality, morbidity, and social problems among youth and adults often are established during youth, extend into adulthood, and are interrelated. The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health risk behaviors among youth and youth adults: behaviors that contribute to unintentional and intentional injuries, tobacco use, alcohol and other drug use, sexual behaviors, dietary behaviors, and physical activity. The YRBSS includes a national, school-based survey conducted by CDC and state and local school-based surveys conducted by state and local education agencies. This report summarizes results from the national survey, 24 state surveys, and nine local surveys conducted among high school students during February through May 1993. In the United States, 72% of all deaths among school-age youth and young adults are from four causes: motor vehicle crashes, other intentional injuries, homicide, and suicide. Results from the 1993 YRBSS suggest many high school students practice behaviors that may increase their likelihood of death from these four causes: 19.1% rarely or never use a safety belt, 35.3% had ridden during the 30 days preceding the survey with a driver who had been drinking alcohol, 22.1% had carried a weapon during the 30 days preceding the survey, 80.9% ever drank alcohol, 32.8% ever used marijuana, and 8.6% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among adolescents also result from unintended pregnancies and sexually transmitted diseases including HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

XASH genes promote neurogenesis in Xenopus embryos.

Neural development in Drosophila is promoted by a family of basic helix-loop-helix (bHLH) transcription factors encoded within the Achaete Scute-Complex (AS-C). XASH-3, a Xenopus homolog of the Drosophila AS-C genes, is expressed during neural induction within a portion of the dorsal ectoderm that gives rise to the neural plate and tube. Here, we show that XASH-3, when expressed with the promiscuous binding partner XE12, specifically activates the expression of neural genes in naive ectoderm, suggesting that XASH-3 promotes neural development. Moreover, XASH-3/XE12 RNA injections into embryos lead to hypertrophy of the neural tube. Interestingly, XASH-3 misexpression does not lead to the formation of ectopic neural tissue in ventral regions, suggesting that the domain of XASH proneural function is restricted in the embryo. In contrast to the neural inducer noggin, which permanently activates the NCAM gene, the activation of neural genes by XASH-3/XE12 is not stable in naive ectoderm, yet XASH-3/XE12 powerfully and stably activates NCAM, Neurofilament and type III beta-tubulin gene expression in noggin-treated ectoderm. These results show that the XASH-3 promotes neural development, and suggest that its activity depends on additional factors which are induced in ectoderm by factors such as noggin.

Animals↗