Search PubMed⌕ Search

Biomedical subjects

W A Harris

Publications and source records attributed to W A Harris.

At least 73 records · Page 4Linked to original sources
PubMed1993

Expression of an extracellular deletion of Xotch diverts cell fate in Xenopus embryos.

Xotch is a Xenopus homolog of Notch, a receptor involved in cell fate decisions in Drosophila. Using an extracellular deletion construct, Xotch delta E, we show that Xotch has a similar role in Xenopus embryos. Broad expression causes the loss of dorsal structures and the expansion and disorganization of the brain. Single blastomere injections of Xotch delta E induce autonomous neural and mesodermal hypertrophy, even in the absence of cell division. Xotch delta E inhibits the early expression of epidermal and neural crest markers yet enhances and extends the response of animal caps to mesodermal and neural induction. Our data suggest a mechanism for the function of Notch homologs in which they delay differentiation and leave undetermined cells competent to respond to later inductive signals.

Animals↗
PubMed1993

Position, guidance, and mapping in the developing visual system.

Positional identity in the visual system affects the topographic projection of the retina onto its central targets. In this review we discuss gradients and positional information in the retina, when and how they arise, and their functional significance in development. When the axons of retinal ganglion cells leave the eye, they navigate through territory in the central nervous system that is rich in positional information. We review studies that explore the navigational cues that the growth cones of retinal axons use to orient towards their target and organize themselves as they make this journey. Finally, these axons arrive at their central targets and make a precise topographic map of visual space that is crucial for adaptive visual behavior. In the last section of this review, we examine the topographic cues in the tectum, what they are, when, and how they arise, and how retinal axons respond to them. We also touch on the role of neural activity in the refinement of this topography.

Animals↗
PubMed1993

Increased production of apolipoprotein A-I associated with elevated plasma levels of high-density lipoproteins, apolipoprotein A-I, and lipoprotein A-I in a patient with familial hyperalphalipoproteinemia.

Familial hyperalphalipoproteinemia (FHA) is a heritable trait associated with elevated plasma concentrations of high-density lipoprotein (HDL) cholesterol and possibly with longevity and protection against coronary heart disease (CHD). The metabolic basis and molecular etiology of FHA have not been established in most kindreds. The proband of a kindred with FHA and possible longevity was found to have elevated plasma levels of HDL cholesterol, apolipoprotein (apo) A-I, and lipoproteins containing apo A-I without apo A-II (Lp A-I), but normal levels of apo A-II and lipoproteins containing apo A-I with apo A-II (Lp A-I:A-II). The in vivo kinetics of apo A-I and apo A-II were studied in the FHA proband and in control subjects using both exogenous radiotracer (125I-apo A-I and 131I-apo A-II) and endogenous stable isotope (primed constant infusion of 13C6-phenylalanine) labeling techniques. The production rate (PR) of apo A-I was markedly increased in the FHA subject (28.9 mg/kg.d) compared with the control subjects (12.0 +/- 2.1 mg/kg.d), whereas the apo A-II PR was not substantially increased. The primary sequence of the proband's apo A-I gene, including 1.2 kb of the 5'-flanking sequence, was normal. We conclude that a selective upregulation of apo A-I production is one metabolic cause of FHA, and results in high plasma concentrations of HDL cholesterol, apo A-I, and Lp A-I and possibly in protection from atherosclerotic CHD.

Apolipoprotein A-I↗
PubMed1993

Navigational errors made by growth cones without filopodia in the embryonic Xenopus brain.

We have developed an exposed brain preparation for observing growth cone pathfinding behavior while performing in vivo pharmacological manipulations, and we used it to test whether Xenopus retinal growth cones need filopodia to navigate. Time-lapse video observation showed that cytochalasin B acted quickly and reversibly when applied; cytochalasin B-treated growth cones lacked filopodia, but had active lamellipodia and continued to advance slowly. Whereas normal retinotectal axons visualized with horseradish peroxidase turn caudally in the mid-diencephalon to reach the tectum, cytochalasin B-treated axons grew past the normal turning point and, instead, continued straight within the diencephalon. In dose-response experiments, pathfinding became abnormal in the same concentration range in which filopodia disappeared. These results suggest that filopodia are necessary for retinal growth cones to respond to guidance signals in the diencephalon.

Animals↗
PubMed1993

XASH1, a Xenopus homolog of achaete-scute: a proneural gene in anterior regions of the vertebrate CNS.

The pro-neural achaete-scute complex (ASC) of Drosophila encodes four homologous proteins, each containing a basic helix-loop-helix (bHLH) domain, characteristic of a large family of transcription factors. We have isolated XASH1, a Xenopus homolog of achaete-scute. The XASH1 protein is very similar to the ASC proteins of Drosophila and the rat homolog, MASH1. XASH1 is expressed in the embryonic anterior central nervous system in a dynamic sequence, first in the midbrain, then in the forebrain, and then in the eye and hindbrain. In the larva, XASH1 expression correlates with regions of continued neurogenesis in the CNS, revealing the pattern of rhombomeres in the hindbrain, and other proliferative zones in the eye and midbrain. As a heterodimer with the bHLH protein E12, XASH1 binds specifically to an enhancer sequence derived from the promoter of the proneural achaete gene of Drosophila. This binding is inhibited by the extramacrochaete protein, a negative regulator of ASC gene function and neurogenesis in Drosophila. The combined evidence described in this paper strongly suggests that XASH1 plays a role in Xenopus neurogenesis similar to that played by the ASC genes in Drosophila.

Amino Acid Sequence↗
PubMed1992

Two cellular inductions involved in photoreceptor determination in the Xenopus retina.

Cellular determination in the Xenopus retina is not a strict consequence of cell lineage or cell birthdate. This suggests that a retinal cell gets its fate by either local cellular interactions, diffusible factors, or an indeterminate stochastic mechanism. We have performed an in vitro experiment in which cellular contact is controlled to test the first possibility directly. We use these experiments to demonstrate that two cellular inductions are involved in photoreceptor determination in vitro and that these inductions also occur during development in the retina in vivo. The first interaction is responsible for biasing cells toward either a generic photoreceptor or a cone fate, while the second directs cells toward a rod cell fate.

Animals↗
PubMed1992

Effect of ascorbic acid supplementation on the sperm quality of smokers.

OBJECTIVE: To determine the effect of ascorbic acid supplementation on the sperm quality of heavy smokers. DESIGN: Microscopic examination of semen for 1 month during supplementation with placebo or ascorbic acid at dose levels of 200 or 1,000 mg/d. SETTING: Department of Obstetrics and Gynecology, The University of Texas Medical Branch. PARTICIPANTS: Seventy-five men (20 to 35 years old) randomly divided into one of three supplementation groups: placebo, 200 mg and 1,000 mg of ascorbic acid. MAIN OUTCOME: Improvement in sperm quality as compared with presupplementation levels and between the three treatment groups. RESULTS: The placebo group showed no improvement in sperm quality. The groups receiving ascorbic acid showed improvement in sperm quality with most improvement in the 1,000-mg group. Pearson's correlation showed statistically significant relationships between the weekly group means of serum and seminal plasma ascorbic acid levels and sperm qualities. CONCLUSIONS: Ascorbic acid supplementation of heavy smokers in excess of 200 mg/d results in improved sperm quality.

Adult↗
PubMed1991

The molecular genetics of invertebrate phototransduction.

Phototransduction, the primary event in the processing of visual stimuli, is the conversion of light energy into a change in the ionic permeabilities of the photoreceptor cell membrane. In both vertebrates and invertebrates, this process is carried out through a specialized form of a G-protein-coupled receptor cascade. The mechanisms that mediate visual excitation in the vertebrate photoreceptor have been physiologically and biochemically well characterized, and many aspects of this system have served as prototypes for other transduction cascades. However, there are still many unresolved issues in vertebrate phototransduction. The study of phototransduction in Drosophila offers a unique opportunity to make use of powerful molecular genetic techniques to identify novel transduction molecules, and then to examine the function of these molecules in vivo, in their normal cellular environment. The results of a combination of molecular, genetic, physiological and biochemical studies are beginning to produce a clearer model for the complex mechanisms involved in invertebrate visual transduction.

Animals↗
PubMed1991

Neuronal determination without cell division in Xenopus embryos.

Cell division in the Xenopus CNS was blocked by incubating embryos in a mixture of the DNA synthesis inhibitors hydroxyurea and aphidicolin. Surprisingly, embryos treated at the beginning of gastrulation proceeded normally through neurulation, neural tube closure, and CNS subdivision. Thus, cell division is not critical for neural induction or early morphogenetic events in the CNS. Neuroblasts in treated embryos differentiated into neurons of many classes, indicating that cellular determination in the CNS can be dissociated from lineage and birth date. Axonal tracts and embryonic reflexes also developed. The remarkable amount of normal CNS development that occurs in these animals may be explained by a series of sequential inductions that are largely independent of cell proliferation.

Animals↗
PubMed1990

Mapping of the presumptive brain regions in the neural plate of Xenopus laevis.

Two cell autonomous fluorescent labels (DiI and Hoechst) were used as vital markers in a fate map study of the Xenopus neural plate and ridge. Most areas of the brain derive from the neural plate in a fate map that is consistent with the topology of a sheet rolling into a tube, i.e., neighboring areas are maintained as neighbors. This has enabled us not only to plot the fates of larval brain structures, but also to suggest their primordial orientation in the neural plate. Since overlapping areas of the plate gave rise to overlapping regions of the central nervous system (CNS), we have been able to construct a space-filling model of the neural plate, whereby the number of founder cells for each brain region fate-mapped may be estimated roughly. Much of the telencephalon, ventral forebrain, and dorsal brain stem derives from the neural ridge and not the neural plate in the stage 15 Xenopus embryo. The structures of the forebrain were examined in detail because there were indications of substantial cell movements in this region. The anterior pituitary arises from the mid-anterior ridge, while hypothalamic structures arise from the midline regions of the anterior neural plate. Consistent groups of ventral hypothalamic structures were labeled when fluorescent markers were applied to these parts of the neural plate, indicating stereotyped cell movements. Detailed comparisons were made between the fate map of the Ambystoma neural plate (Jacobson, 1959) and that of Xenopus.

Animals↗
PubMed1989

Local positional cues in the neuroepithelium guide retinal axons in embryonic Xenopus brain.

Growing retinal axons home to their distant target, the tectum, even when they are displaced from their normal pathway. This argues for long-range guidance mechanisms in the embryonic brain. Growth cones may orientate to diffusible attractants released from the target, as proposed in other systems, or they may use a stable distribution of positional information in the neuroepithelium. To distinguish between these possibilities, small pieces of the presumptive optic tract, through which retinal axons will normally grow, were rotated by approximately 90 degrees either clockwise or counterclockwise. When the retinal axons later encountered the rotated neuroepithelium, they also turned clockwise or counterclockwise, in correspondence with the direction of rotation. This demonstrates that long-range navigation of retinal axons in the vertebrate brain is based partly on stable, local positional factors, rather than on remote diffusible factors.

Animals↗
PubMed1989

Growth cone interactions with a glial cell line from embryonic Xenopus retina.

We have isolated a nonneuronal cell line from Xenopus retinal neuroepithelium (XR1 cell line). On the basis of immunocytochemical characterization using monoclonal antibodies generated in our laboratory as well as several other glial-specific antibodies, we have established that the XR1 cells are derived from embryonic astroglia. A monolayer of XR1 cells serves as an excellent substrate upon which embryonic retinal explants attach and elaborate neurites. This neurite outgrowth promoting activity appears not to be secreted into the medium, as medium conditioned by XR1 cells is ineffective in promoting outgrowth. Cell-free substrates were prepared to examine whether outgrowth promoting activity is also associated with the XR1 extracellular matrix (ECM). Substrates derived from XR1 cells grown on collagen are still capable of promoting outgrowth following osmotic shock and chemical extraction. This activity does not appear to be associated with laminin or fibronectin. Scanning electron microscopy was used to examine growth cones of retinal axons on XR1 cells and other substrates that supported neurite outgrowth. Growth cones and neurites growing on a monolayer of XR1 cells, or on collagen conditioned by XR1 cells, closely resemble the growth cones of retinal ganglion cells in vivo. A polyclonal antiserum (NOB1) generated against XR1 cells effectively and specifically inhibits neurite outgrowth on XR1-conditioned collagen. We therefore propose that neurite outgrowth promoting factors produced by these cells are associated with the extracellular matrix and may be glial specific.

Animals↗