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James W Walters

Publications and source records attributed to James W Walters.

8 recordsLinked to original sources
PubMed2006

FoxD3 regulation of Nodal in the Spemann organizer is essential for Xenopus dorsal mesoderm development.

Induction and patterning of the mesodermal germ layer is a key early step of vertebrate embryogenesis. We report that FoxD3 function in the Xenopus gastrula is essential for dorsal mesodermal development and for Nodal expression in the Spemann organizer. In embryos and explants, FoxD3 induced mesodermal genes, convergent extension movements and differentiation of axial tissues. Engrailed-FoxD3, but not VP16-FoxD3, was identical to native FoxD3 in mesoderm-inducing activity, indicating that FoxD3 functions as a transcriptional repressor to induce mesoderm. Antagonism of FoxD3 with VP16-FoxD3 or morpholino-knockdown of FoxD3 protein resulted in a complete block to axis formation, a loss of mesodermal gene expression, and an absence of axial mesoderm, indicating that transcriptional repression by FoxD3 is required for mesodermal development. FoxD3 induced mesoderm in a non-cell-autonomous manner, indicating a role for secreted inducing factors in the response to FoxD3. Consistent with this mechanism, FoxD3 was necessary and sufficient for the expression of multiple Nodal-related genes, and inhibitors of Nodal signaling blocked mesoderm induction by FoxD3. Therefore, FoxD3 is required for Nodal expression in the Spemann organizer and this function is essential for dorsal mesoderm formation.

Animals↗
PubMed2006

Planar polarization of the denticle field in the Drosophila embryo: roles for Myosin II (zipper) and fringe.

Epithelial planar cell polarity (PCP) allows epithelial cells to coordinate their development to that of the tissue in which they reside. The mechanisms that impart PCP as well as effectors that execute the polarizing instructions are being sought in many tissues. We report that the epidermal epithelium of Drosophila embryos exhibits PCP. Cells of the prospective denticle field, but not the adjacent smooth field, align precisely. This requires Myosin II (zipper) function, and we find that Myosin II is enriched in a bipolar manner, across the parasegment, on both smooth and denticle field cells during denticle field alignment. This implies that actomyosin contractility, in combination with denticle-field-specific effectors, helps execute the cell rearrangements involved. In addition to this parasegment-wide polarity, prospective denticle field cells express an asymmetry, uniquely recognizing one cell edge over others as these cells uniquely position their actin-based protrusions (ABPs; which comprise each denticle) at their posterior edge. Cells of the prospective smooth field appear to be lacking proper effectors to elicit this unipolar response. Lastly, we identify fringe function as a necessary effector for high fidelity placement of ABPs and show that Myosin II (zipper) activity is necessary for ABP placement and shaping as well.

Actins↗
PubMed2005

Serrate-Notch signaling defines the scope of the initial denticle field by modulating EGFR activation.

The Drosophila embryonic epidermis has been a key model for understanding the establishment of cell type diversity across a cellular field. During segmental patterning, distinct signaling territories are established that employ either the Hedgehog, Spitz, Serrate or Wingless ligands. How these pathways control segmental pattern is not completely clear. One major decision occurs as cells are allocated to differentiate either smooth cuticle or denticle type cuticle. This allocation is based on competition between Wingless signaling and Spitz, which activates the Epidermal Growth Factor Receptor (EGFR). Here we show that a main role for Serrate-Notch signaling is to adjust the Spitz signaling domain. Serrate accomplishes this task by activating Notch in a discrete domain, the main purpose of which is to broaden the spatially regulated expression of Rhomboid. This adjusts the breadth of the source for Spitz, since Rhomboid is necessary for the production of active Spitz. We also show that the Serrate antagonist, fringe, must temper Notch activity to insure that the activation of the EGFR is not too robust. Together, Serrate and Fringe modulate Notch activation to generate the proper level of EGFR activation. If Serrate-Notch signaling is absent, the denticle field narrows while the smooth cell field expands, as judged by the expression of the denticle field determinant Ovo/Shaven baby. This establishes one important role for the Serrate signaling territory, which is to define the extent of denticle field specification.

Animals↗
PubMed1992

Proximate personhood as a standard for making difficult treatment decisions: imperiled newborns as a case study.

... The standard of personhood is gaining increased attention and prominence. The essential claim is that only individuals with capacities for significant cerebral functioning possess a morally unique claim to existence. Persons are defined as individuals who are self-aware and capable of self-direction (Engelhardt), able to enter meaningful relationships (McCormick), capable of minimal independent existence (Shelp), and in possession of a minimal 20-40 I.Q. (Joseph Fletcher). These are "high standard" personhood positions (those holding higher-brain related criteria). It is a commonplace with most such positions that newborns -- all newborns -- are not, strictly speaking, persons. That is, newborns are not self-aware, intentionally choosing individuals.... The thesis of this essay is that a developing individual's right to life increases as he or she approaches the threshold of personal life. That is, the more a newborn approximates -- or is proximate to -- undisputed personhood (e.g. the status of readers of this essay), the greater his or her claim to life. The two pivotal criteria for determining personhood are the potentiality for and development toward becoming an undisputed personal being. I am presupposing, for purposes of argument, that the handicapped infant would not be an excessive familial burden or an inordinate financial load for society, one an ancient and the other a modern criterion. That condition granted, this essay contends that if an imperiled newborn is reasonably projected to reach at least minimal personal capacity, treatment should be given.

Abortion, Induced↗
PubMed1991

Anencephalic infants as organ sources.

Liveborn anencephalic infants cannot be used legally as sources for vital organs in the United States and Canada. Understandably, knowledgeable physicians and bioethicists are divided over the ethics of such use and hold various views on whether the legal status of anencephalic newborns should ever be changed. Even if anencephalic newborns could be utilized as organ sources, at best a few hundred infants needing transplant organs would be saved each year. Primarily, this is because the number of anencephalic newborns is likely to diminish due to prenatal diagnosis resulting in abortions. However, the case of anencephalic infants and their treatment is paradigmatic in raising questions far beyond mere organ transplantation.... This analytical report is given against the backdrop of a burgeoning medical technology which can sustain human life far beyond that generally regarded as a meaningful, functional life. The report has three sections: first, a description of the approaches to the use of anencephalic infants in North America over the last five years; second, a summary of the results of a survey of informed clinicians and ethicists; and third, an indication of the leading ethical issues raised by human individuals at the border of life.

Anencephaly↗