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William A Harris

Publications and source records attributed to William A Harris.

At least 19 recordsLinked to original sources
PubMed2006

Hedgehog signaling and the retina: insights into the mechanisms controlling the proliferative properties of neural precursors.

Hedgehog signaling has been linked to cell proliferation in a variety of systems; however, its effects on the cell cycle have not been closely studied. In the vertebrate retina, Hedgehog's effects are controversial, with some reports emphasizing increased proliferation and others pointing to a role in cell cycle exit. Here we demonstrate a novel role for Hedgehog signaling in speeding up the cell cycle in the developing retina by reducing the length of G1 and G2 phases. These fast cycling cells tend to exit the cell cycle early. Conversely, retinal progenitors with blocked Hedgehog signaling cycle more slowly, with longer G1 and G2 phases, and remain in the cell cycle longer. Hedgehog may modulate cell cycle kinetics through activation of the key cell cycle activators cyclin D1, cyclin A2, cyclin B1, and cdc25C. These findings support a role for Hedgehog in regulating the conversion from slow cycling stem cells to fast cycling transient amplifying progenitors that are closer to cell cycle exit.

Animals↗
PubMed2006

Polarization and orientation of retinal ganglion cells in vivo.

In the absence of external cues, neurons in vitro polarize by using intrinsic mechanisms. For example, cultured hippocampal neurons extend arbitrarily oriented neurites and then one of these, usually the one nearest the centrosome, begins to grow more quickly than the others. This neurite becomes the axon as it accumulates molecular components of the apical junctional complex. All the other neurites become dendrites. It is unclear, however, whether neurons in vivo, which differentiate within a polarized epithelium, break symmetry by using similar intrinsic mechanisms. To investigate this, we use four-dimensional microscopy of developing retinal ganglion cells (RGCs) in live zebrafish embryos. We find that the situation is indeed very different in vivo, where axons emerge directly from uniformly polarized cells in the absence of other neurites. In vivo, moreover, components of the apical complex do not localize to the emerging axon, nor does the centrosome predict the site of axon emergence. Mosaic analysis in four dimensions, using mutants in which neuroepithelial polarity is disrupted, indicates that extrinsic factors such as access to the basal lamina are critical for normal axon emergence from RGCs in vivo.

Animals↗
PubMed2006

Lineage in the vertebrate retina.

Recent results are changing the way we think about cell-fate decision mechanisms in the retina. For a long time it was accepted that lineage was not important in retinal cellular determination but, as we review here, new data show that lineage programmes might be at the heart of this process. These programmes are intrinsic, but they are also plastic and are influenced by extrinsic signals.

Animals↗
PubMed2006

Youth risk behavior surveillance--United States, 2005.

PROBLEM: Priority health-risk behaviors, which contribute to the leading causes of morbidity and mortality among youth and adults, often are established during childhood and adolescence, extend into adulthood, are interrelated, and are preventable. REPORTING PERIOD COVERED: October 2004-January 2006. DESCRIPTION OF THE SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults, including behaviors that contribute to unintentional injuries and violence; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infections; unhealthy dietary behaviors; and physical inactivity. In addition, the YRBSS monitors general health status and the prevalence of overweight and asthma. YRBSS includes a national school-based survey conducted by CDC and state and local school-based surveys conducted by state and local education and health agencies. This report summarizes results from the national survey, 40 state surveys, and 21 local surveys conducted among students in grades 9-12 during October 2004-January 2006. RESULTS: In the United States, 71% of all deaths among persons aged 10-24 years result from four causes: motor-vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 2005 national Youth Risk Behavior Survey (YRBS) indicated that, during the 30 days preceding the survey, many high school students engaged in behaviors that increased their likelihood of death from these four causes: 9.9% had driven a car or other vehicle when they had been drinking alcohol; 18.5% had carried a weapon; 43.3% had drunk alcohol; and 20.2% had used marijuana. In addition, during the 12 months preceding the survey, 35.9% of high school students had been in a physical fight and 8.4% had attempted suicide. Substantial morbidity and social problems among youth also result from unintended pregnancies and STDs, including HIV infection. During 2005, a total of 46.8% of high school students had ever had sexual intercourse; 37.2% of sexually active high school students had not used a condom at last sexual intercourse; and 2.1% had ever injected an illegal drug. Among adults aged >/=25 years, 61% of all deaths result from two causes: cardiovascular disease and cancer. Results from the 2005 national YRBS indicated that risk behaviors associated with these two causes of death were initiated during adolescence. During 2005, a total of 23.0% of high school students had smoked cigarettes during the 30 days preceding the survey; 79.9% had not eaten >/=5 times/day of fruits and vegetables during the 7 days preceding the survey; 67.0% did not attend physical education classes daily; and 13.1% were overweight. INTERPRETATION: Since 1991, the prevalence of many health-risk behaviors among high school students nationwide has decreased. However, many high school students continue to engage in behaviors that place them at risk for the leading causes of mortality and morbidity. The prevalence of many health-risk behaviors varies across cities and states. PUBLIC HEALTH ACTION: YRBS data are used to measure progress toward achieving 15 national health objectives for Healthy People 2010 and three of the 10 leading health indicators, to assess trends in priority health-risk behaviors among high school students, and to evaluate the impact of broad school and community interventions at the national, state, and local levels. More effective school health programs and other policy and programmatic interventions are needed to reduce risk and improve health outcomes among youth.

Adolescent↗
PubMed2006

Expression of Xenopus laevis Lhx2 during eye development and evidence for divergent expression among vertebrates.

Members of the LIM homeodomain (LIM-HD) family of proteins are double zinc-finger containing transcription factors with important functions in pattern formation and cell lineage determination. The LIM-HD family member Lhx2 is required for normal eye, liver, and central nervous system formation. Lhx2(-/-) mice lack eyes, and experiments in Xenopus predict that Lhx2 forms a regulatory network with other eye field transcription factors to specify the eye field during eye formation. Here, we describe the structure and developmental expression pattern of the Xenopus laevis homologue, XLhx2. We show that XLhx2 shares significant amino acid sequence identity with other vertebrate Lhx2 proteins and Drosophila apterous (ap). The expression patterns of XLhx2 in the early neural plate and during eye development are consistent with a role in eye field specification and retinal differentiation. Despite highly similar expression patterns in the mouse and Xenopus central nervous system, divergent expression patterns were also observed. Phylogenetic analysis confirmed the identity of the isolated cDNA as a Xenopus ortholog of Lhx2. Therefore, in spite of structural similarities, the mouse and Xenopus Lhx2 expression patterns differ, suggesting potential functional differences in these species.

Amino Acid Sequence↗
PubMed2006

Mechanisms of ventral patterning in the vertebrate nervous system.

Dorsoventral patterning of the neural tube has a crucial role in shaping the functional organization of the CNS. It is well established that hedgehog signalling plays a key role in specifying ventral cell types throughout the neuroectoderm, and major progress has been made in elucidating how hedgehog signalling works in this ventral specification. In addition, other molecular pathways, including nodal, retinoic acid and fibroblast growth factor signalling, have been identified as important molecular cues for ventral patterning of the spinal cord, telencephalon and eye. Here, we discuss recent advances in this field, highlighting the emerging interplay of these signalling pathways in the molecular specification of ventral patterning at different rostrocaudal levels of the CNS.

Animals↗
PubMed2006

Youth risk behavior surveillance--United States, 2005.

In the United States, 71% of all deaths among persons aged 10-24 years result from 4 causes: motorvehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 2005 national Youth Risk Behavior Survey (YRBS) indicated that during the 30 days preceding the survey, many high school students engaged in behaviors that increased their likelihood of death from these 4 causes: 9.9% had driven a car or other vehicle when they had been drinking alcohol, 18.5% had carried a weapon, 43.3% had drunk alcohol, and 20.2% had used marijuana. In addition, during the 12 months preceding the survey, 35.9% of high school students had been in a physical fight and 8.4% had attempted suicide. Substantial morbidity and social problems among youth also result from unintended pregnancies and sexually transmitted diseases, including human immunodeficiency virus infection. During 2005, a total of 46.8% of high school students had ever had sexual intercourse, 37.2% of sexually active high school students had not used a condom at last sexual intercourse, and 2.1% had ever injected an illegal drug. Among adults aged > or =25 years, 61% of all deaths result from 2 causes: cardiovascular disease and cancer. Results from the 2005 national YRBS indicated that risk behaviors associated with these 2 causes of death were initiated during adolescence. During 2005, a total of 23.0% of high school students had smoked cigarettes during the 30 days preceding the survey, 79.9% had not eaten > or =5 times/day of fruits and vegetables during the 7 days preceding the survey, 67.0% did not attend physical education classes daily, and 13.1% were overweight.

Adolescent↗
PubMed2005

Influences on neural lineage and mode of division in the zebrafish retina in vivo.

Cell determination in the retina has been under intense investigation since the discovery that retinal progenitors generate clones of apparently random composition (Price, J., D. Turner, and C. Cepko. 1987. Proc. Natl. Acad. Sci. USA. 84:156-160; Holt, C.E., T.W. Bertsch, H.M. Ellis, and W.A. Harris. 1988. Neuron. 1:15-26; Wetts, R., and S.E. Fraser. 1988. Science. 239:1142-1145). Examination of fixed tissue, however, sheds little light on lineage patterns or on the relationship between the orientation of division and cell fate. In this study, three-dimensional time-lapse analyses were used to trace lineages of retinal progenitors expressing green fluorescent protein under the control of the ath5 promoter. Surprisingly, these cells divide just once along the circumferential axis to produce two postmitotic daughters, one of which becomes a retinal ganglion cell (RGC). Interestingly, when these same progenitors are transplanted into a mutant environment lacking RGCs, they often divide along the central-peripheral axis and produce two RGCs. This study provides the first insight into reproducible lineage patterns of retinal progenitors in vivo and the first evidence that environmental signals influence the orientation of cell division and the lineage of neural progenitors.

Animals↗
PubMed2005

Tsukushi controls ectodermal patterning and neural crest specification in Xenopus by direct regulation of BMP4 and X-delta-1 activity.

In Xenopus, ectodermal patterning depends on a mediolateral gradient of BMP signaling, higher in the epidermis and lower in the neuroectoderm. Neural crest cells are specified at the border between the neural plate and the epidermis, at intermediate levels of BMP signaling. We recently described a novel secreted protein, Tsukushi (TSK), which works as a BMP antagonist during chick gastrulation. Here, we report on the Xenopus TSK gene (X-TSK), and show that it is involved in neural crest specification. X-TSK expression accumulates after gastrulation at the anterior-lateral edges of the neural plate, including the presumptive neural crest region. In gain-of-function experiments, X-TSK can strongly enhance neural crest specification by the dorsolateral mesoderm or X-Wnt8 in ectodermal explants, while the electroporation of X-TSK mRNA in the lateral ectoderm of embryos after gastrulation can induce the expression of neural crest markers in vivo. By contrast, depletion of X-TSK in explants or embryos impairs neural crest specification. Similarly to its chick homolog, X-TSK works as a BMP antagonist by direct binding to BMP4. However, X-TSK can also indirectly regulate BMP4 mRNA expression at the neural plate border via modulation of the Delta-Notch signaling pathway. We show that X-TSK directly binds to the extracellular region of X-delta-1, and modulates Delta-dependent Notch activity. We propose that X-TSK plays a key role in neural crest formation by directly regulating BMP and Delta activities at the boundary between the neural and the non-neural ectoderm.

Animals↗
PubMed2005

Two of these or two of those?

Symmetrically dividing neuroepithelial cells may produce two daughters that are both proliferating or both postmitotic, as highlighted by Zigman et al. in this issue of Neuron and Sanada and Tsai in a recent issue of Cell. Here, I will attempt to offer a simple explanation why these results may be so different.

Animals↗
PubMed2005

Time-lapse analysis of retinal differentiation.

The availability of new vital markers and the improvements in time-lapse video microscopy have increased our ability to observe developmental events in the retina while they are happening. Using this approach, advances have been made in the understanding of important issues such as how division patterns relate to cell fate determination, how post-mitotic progenitors reach their correct retinal layers, and finally, how retinal ganglion cell axons navigate out of the retina and to their final targets in the midbrain.

Animals↗
PubMed2005

MALDI of individual biomolecule-containing airborne particles in an ion trap mass spectrometer.

Individual airborne biomolecule-containing particles were detected and characterized in near real-time by matrix-assisted laser desorption/ionization (MALDI) with an ion trap mass spectrometer. Biomolecule-containing particles were laboratory-generated and passed through a heated region containing a solution of matrix in equilibrium with the gas phase. Passage into a cooler region created a supersaturation, resulting in rapid deposition of the matrix vapor onto the biomolecule-containing particles, whereupon they were sampled into the inlet of our spectrometer. The coated particles were collimated and individually sized by light-scattering-based time-of-flight. When the sized particle reached the center of the ion trap, it was irradiated with a focused 266-nm laser, and the resulting ions were mass-analyzed. Mass spectra of leucine enkephalin, bradykinin, substance P, and polylysine-containing particles were determined with attomole sensitivity. Structural information of the peptides contained in an individual particle was obtained by tandem mass spectrometry. Analysis of the results yields insights into the aerosol laser ablation ionization process that suggests an optically limited mechanism for ion production that has interesting ramifications on the utility of aerosol-based MALDI as an analytical technique.

Air↗
PubMed2005

Frizzled 5 signaling governs the neural potential of progenitors in the developing Xenopus retina.

Progenitors in the developing central nervous system acquire neural potential and proliferate to expand the pool of precursors competent to undergo neuronal differentiation. The formation and maintenance of neural-competent precursors are regulated by SoxB1 transcription factors, and evidence that their expression is regionally regulated suggests that specific signals regulate neural potential in subdomains of the developing nervous system. We show that the frizzled (Fz) transmembrane receptor Xfz5 selectively governs neural potential in the developing Xenopus retina by regulating the expression of Sox2. Blocking either Xfz5 or canonical Wnt signaling within the developing retina inhibits Sox2 expression, reduces cell proliferation, inhibits the onset of proneural gene expression, and biases individual progenitors toward a nonneural fate, without altering the expression of multiple progenitor markers. Blocking Sox2 function mimics these effects. Rescue experiments indicate that Sox2 is downstream of Xfz5. Thus, Fz signaling can regulate the neural potential of progenitors in the developing nervous system.

Animals↗
PubMed2005

Endocytosis-dependent desensitization and protein synthesis-dependent resensitization in retinal growth cone adaptation.

It has been proposed that growth cones navigating through gradients adapt to baseline concentrations of guidance cues. This adaptation process is poorly understood. Using the collapse assay, we show that adaptation in Xenopus laevis retinal growth cones to the guidance cues Sema3A or netrin-1 involves two processes: a fast, ligand-specific desensitization that occurs within 2 min of exposure and is dependent on endocytosis, and a slower, ligand-specific resensitization, which occurs within 5 min and is dependent upon protein synthesis. These two phases of adaptation allow retinal axons to adjust their range of sensitivity to specific guidance cues.

Adaptation, Biological↗
PubMed2005

Dorsoventral patterning of the Xenopus eye: a collaboration of Retinoid, Hedgehog and FGF receptor signaling.

In the developing spinal cord and telencephalon, ventral patterning involves the interplay of Hedgehog (Hh), Retinoic Acid (RA) and Fibroblast Growth Factor (FGF) signaling. In the eye, ventral specification involves Hh signaling, but the roles of RA and FGF signaling are less clear. By overexpression assays in Xenopus embryos, we found that both RA and FGF receptor (FGFR) signaling ventralize the eye, by expanding optic stalk and ventral retina, and repressing dorsal retina character. Co-overexpression experiments show that RA and FGFR can collaborate with Hh signaling and reinforce its ventralizing activity. In loss-of-function experiments, a strong eye dorsalization was observed after triple inhibition of Hh, RA and FGFR signaling, while weaker effects were obtained by inhibiting only one or two of these pathways. These results suggest that the ventral regionalization of the eye is specified by interactions of Hh, RA and FGFR signaling. We argue that similar mechanisms might control ventral neural patterning throughout the central nervous system.

Animals↗
PubMed2004

Youth risk behavior surveillance--United States, 2003.

PROBLEM/CONDITION: Priority health-risk behaviors, which contribute to the leading causes of morbidity and mortality among youth and adults, often are established during youth, extend into adulthood, are interrelated, and are preventable. REPORTING PERIOD: This report covers data collected during February-December 2003. 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 injuries and violence; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection; unhealthy dietary behaviors; and physical inactivity--plus overweight. YRBSS includes a national school-based survey conducted by CDC as well as state and local school-based surveys conducted by education and health agencies. This report summarizes results from the national survey, 32 state surveys, and 18 local surveys conducted among students in grades 9-12 during February-December 2003. RESULTS AND INTERPRETATION: In the United States, 70.8% of all deaths among persons aged 10-24 years result from only four causes: motor-vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 2003 national Youth Risk Behavior Survey demonstrated that, during the 30 days preceding the survey, numerous high school students engage in behaviors that increase their likelihood of death from these four causes: 30.2% had ridden with a driver who had been drinking alcohol; 17.1% had carried a weapon; 44.9% had drunk alcohol; and 22.4% had used marijuana. In addition, during the 12 months preceding the survey, 33.0% of high school students had been in a physical fight, and 8.5% had attempted suicide. Substantial morbidity and social problems among young persons also result from unintended pregnancies and STDs, including HIV infection. In 2003, 46.7% of high school students had ever had sexual intercourse; 37% of sexually active students had not used a condom at last sexual intercourse; and 3.2% had ever injected an illegal drug. Among adults aged > or =25 years, 62.9% of all deaths results from two causes: cardiovascular diseases and cancer. Results from the 2003 national Youth Risk Behavior Survey demonstrate that the majority of risk behaviors associated with these two causes of death are initiated during adolescence. In 2003, a total of 21.9% of high school students had smoked cigarettes during the 30 days preceding the survey; 78% had not eaten > or =5 servings/day of fruits and vegetables during the 7 days preceding the survey; 33.4% had participated in an insufficient amount of physical activity; and 13.5% were overweight. ACTIONS TAKEN: YRBSS data are being used to measure progress toward achieving 15 national health objectives for 2010 and three of the 10 leading health indicators. In addition, education and health officials at national, state, and local levels are using these YRBSS data to improve policies and programs to reduce priority health-risk behaviors among youth.

Adolescent↗
PubMed2004

Tsukushi functions as an organizer inducer by inhibition of BMP activity in cooperation with chordin.

During chick gastrulation, inhibition of BMP signaling is required for primitive streak formation and induction of Hensen's node. We have identified a unique secreted protein, Tsukushi (TSK), which belongs to the Small Leucine-Rich Proteoglycan (SLRP) family and is expressed in the primitive streak and Hensen's node. Grafts of cells expressing TSK in combination with the middle primitive streak induce an ectopic Hensen's node, while electroporation of TSK siRNA inhibits induction of the node. In Xenopus embryos, TSK can block BMP function and induce a secondary dorsal axis, while it can dorsalize ventral mesoderm and induce neural tissue in embryonic explants. Biochemical analysis shows that TSK binds directly to both BMP and chordin and forms a ternary complex with them. These observations indicate that TSK is an essential dorsalizing factor involved in the induction of Hensen's node.

Amino Acid Sequence↗