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L Redmond

Publications and source records attributed to L Redmond.

9 recordsLinked to original sources

The role of Notch and Rho GTPase signaling in the control of dendritic development.

Dendritic patterning exerts a profound influence on neuronal connectivity. Recent studies indicate that mammalian Notch receptors are expressed by postmitotic neurons and that Notch signaling has a considerable influence on dendritic growth and branching. Investigations into the intracellular effectors of dendritic development have revealed that dendritic growth and branching are differentially affected by activation of the Rho-family GTPases, RhoA, Rac1, and Cdc42. These observations suggest that the differential activation of Notch receptors and Rho-family GTPases by extracellular signals may be important in the generation of morphological diversity in the developing nervous system.

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Palliative care.

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Caregivers↗

Nuclear Notch1 signaling and the regulation of dendritic development.

To understand the function of Notch in the mammalian brain, we examined Notch1 signaling and its cellular consequences in developing cortical neurons. We found that the cytoplasmic domain of endogenous Notch1 translocated to the nucleus during neuronal differentiation. Notch1 cytoplasmic-domain constructs transfected into cortical neurons were present in multiple phosphorylated forms, localized to the nucleus and could induce CBF1-mediated transactivation. Molecular perturbation experiments suggested that Notch1 signaling in cortical neurons promoted dendritic branching and inhibited dendritic growth. These observations show that Notch1 signaling to the nucleus exerts an important regulatory influence on the specification of dendritic morphology in neurons.

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Cues intrinsic to the spinal cord determine the pattern and timing of primary afferent growth.

We have used organotypic cultures of embryonic rat spinal cord and dorsal root ganglia (DRG) to study the development of central projections of primary sensory afferent axons that express calcitonin gene-related peptide (CGRP). In vivo, small- and medium-diameter CGRP-positive primary afferents terminate in laminae I, II, and V of the spinal cord and do not enter the ventral horn. A similar pattern of CGRP-positive axonal projections was observed in spinal cord slices of Day 16 embryos (E16) maintained in culture for 6 days. Both intact and dissociated DRG neurons showed the same pattern of central arborization, indicating that complex intercellular interactions between DRG neurons are not required for laminar specific targeting. Furthermore, targeting to the dorsal horn and avoidance of the ventral horn was observed in isolated dorsal and ventral hemicords, suggesting that separate mechanisms mediate the avoidance of CGRP-positive axons from the ventral horn and the elaboration of the afferent arbors within the dorsal horn. CGRP-positive afferents can grow into the dorsal horn only during a brief time window. Cultures of age-matched (isochronic) DRG and spinal cord from E14, E16, and E18 animals showed the characteristic pattern of CGRP-positive axon arborization, while cultures from E20 and neonatal animals did not. Heterochronic cultures indicate that it is the age of the spinal cord, and not the age of the DRG, that determines the ability of the CGRP-positive afferents to arborize within the dorsal horn. Together these results demonstrate that cues intrinsic to the spinal cord can direct sensory projections to appropriate locations in the spinal cord.

Aging↗

The divergent homeobox gene PBX1 is expressed in the postnatal subventricular zone and interneurons of the olfactory bulb.

In the mammalian brain, an important phase of neurogenesis occurs postnatally in the subventricular zone (SVZ). This region consists of a heterogeneous population of cells, some mitotically active, others postmitotic. A subset of mitotically active SVZ precursor cells gives rise to a population of neurons that migrates over a long distance to their final destination, the olfactory bulb. Other SVZ precursor cells continue to proliferate or undergo cell death. The combination of genes that regulates proliferation and cell fate determination of SVZ precursor cells remains to be identified. We have used the rat homolog of the human homeobox gene PBX1 in Northern analysis and in situ hybridization studies to determine the temporal and regional localization of PBX1 expression during embryonic and postnatal rat brain development. PBX1 is expressed embryonically in the telencephalon. In addition, it is expressed at high levels postnatally in the SVZ, in the migratory pathway to the olfactory bulb, and in the layers of the olfactory bulb that are the targets of these migratory neurons. Combining in situ hybridization for PBX1 with immunostaining for markers of cell proliferation (PCNA), postmitotic neurons (class III beta-tubulin), and glia (GFAP), we show that SVZ proliferating cells and their neuronal progeny express rat PBX1 mRNA, whereas glial cells do not express detectable levels of PBX1. The expression of PBX1 in SVZ precursor cells and postmitotic neurons suggests a role for PBX1 in the generation of olfactory bulb interneurons and in mammalian neurogenesis.

Aging↗

Dieting severity and gastrointestinal symptoms in college women.

Young women report symptoms associated with irritable bowel syndrome (IBS), such as pain, bloating, and changes in bowel movements, more often than young men. Young women with eating disorders also report these gastrointestinal symptoms frequently. We hypothesized that if dieting behaviors were associated with these symptoms, the prevalence and frequency of the symptoms would be positively related to dieting severity in young women. We interviewed 301 1st-year college women representing the continuum of dieting severity. We found that severity of dieting was positively related to frequency of abdominal pain, bloating, diarrhea, and constipation, and that the women who reported 3 or more symptoms regularly scored higher on a scale for dieting severity. Although this study did not examine the relationship between dieting severity and clinical IBS, the findings suggested that dieting is associated with gastrointestinal symptoms in young women.

Comorbidity↗

Identification of nuclear proteins that are developmentally regulated in embryonic rat brain.

To identify nuclear proteins that might play a role in the acquisition of neuronal phenotype, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) was used to analyze nuclear proteins expressed over the course of embryonic rat brain development. Metabolically labeled rat brain nuclear proteins from embryonic day 14 (E14) were compared with proteins from embryonic day 20 (E20). Over this period, the rat brain develops from a collection of relatively homogeneous precursor cells into a complex structure containing many different classes of neurons. Computer-assisted analysis of 2D-PAGE fluorograms identified 11 proteins that show increases in their rate of synthesis between E14 and E20. Twenty proteins that consistently appear at E20 are not detectable on fluorograms of E14 nuclear proteins, even after long exposures, and thus may be considered to appear de novo. Fifty-eight proteins show consistent down-regulation between E14 and E20, and of these, 19 are not detectable on fluorograms of E20 nuclear proteins. The electrophoretic properties of many of these proteins suggest that they are previously unreported, developmentally regulated nuclear proteins. Some of the developmentally regulated, brain-enriched nuclear proteins identified here may play a role in regulating the expression of neural genes important for cellular differentiation in the mammalian CNS.

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