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K D Patterson

Publications and source records attributed to K D Patterson.

At least 19 recordsLinked to original sources
PubMed2000

Distinct expression patterns for two Xenopus Bar homeobox genes.

The BarH1 and BarH2 homeobox genes are coexpressed in cells of the fly retina and in the central and peripheral nervous systems. The fly Bar genes are required for normal development of the eye and external sensory organs. In Xenopus we have identified two distinct vertebrate Bar-related homeobox genes, XBH1 and XBH2. XBH1 is highly related in sequence and expression pattern to a mammalian gene, MBH1, suggesting that they are orthologues. XBH2 has not previously been identified but is clearly related to the Drosophila Bar genes. During early Xenopus embryogenesis XBH1 and XBH2 are expressed in overlapping regions of the central nervous system. XBH1, but not XBH2, is expressed in the developing retina. By comparing the expression of XBH1 with that of hermes, a marker of differentiated retinal ganglion cells, we show that XBH1 is expressed in retinal ganglion cells during the differentiation process, but is down-regulated as cells become terminally differentiated.

Amino Acid Sequence↗
PubMed2000

Embryonic origins of spleen asymmetry.

The spleen is a vertebrate organ that has both hematopoietic and immunologic function. The embryonic origins of the spleen are obscure, with most studies describing the earliest rudiment of the spleen as a condensation of mesodermal mesenchyme on the left side of the dorsal mesogastrium. The development of spleen handedness has not been described previously, presumably because of the difficulty in assaying spleen position in the embryo and the lack of early, organ-specific molecular markers. Here we show that expression of the homeobox gene Nkx2-5 serves as a marker for spleen precursor tissue. Pre-splenic tissue is initially located in symmetric domains on both sides of the embryo but, during subsequent development, only the left side goes on to form the mature spleen. Therefore, the final location of the spleen on the left side of the body axis appears to result from preferential development of the spleen precursor cells on the left side of the embryo. Our studies indicate that the spleen and heart become asymmetric via different cellular mechanisms. Nkx2-5 may function locally as part of the laterality cascade, downstream of nodal and Pitx2, or it may direct asymmetric morphogenesis after laterality has been determined.

Animals↗
PubMed1999

Hox11-family genes XHox11 and XHox11L2 in xenopus: XHox11L2 expression is restricted to a subset of the primary sensory neurons.

The mouse genome contains a small family of homeobox genes related to Hox11, but relatively little is known about the expression of these genes during early development. Hox11 itself is expressed in the embryonic spleen, among other tissues, and is required for its formation. No description of Hox11L2 expression has been presented previously. We have isolated the Xenopus orthologs of Hox11 and Hox11L2 and have carefully compared their expression patterns during embryogenesis. The localization of Xhox11 transcripts in the branchial arches, cranial sensory ganglia and spinal cord is similar, but not identical, to that of mouse Hox11. Xhox11 expression is not detected in the developing spleen. XHox11L2 is expressed exclusively in a portion of the primary sensory system in the frog embryo, including the cranial sensory ganglia and the Rohon-Beard sensory neurons. There is significant overlap in the patterns of Xhox11 and XHox11L2 expression in the spinal cord and cranial sensory ganglia during early development, suggesting that they may function redundantly in these tissues. The timing of Xhox11 and Xhox11L2 expression indicates that Hox11-family members may participate in the final stages of the differentiation process.

Amino Acid Sequence↗
PubMed1998

Homeobox genes in cardiovascular development.

As summarized earlier, a surprisingly large number of different homeobox genes are expressed in the developing heart. Some are clearly important, as demonstrated by mouse gene ablation studies. For example, knockout of Nkx2-5 or Hoxa-3 function is embryonic lethal due to defects in cardiovascular development. However, gene ablation studies indicate that other homeobox genes that show cardiovascular expression are either not required for heart development or their function is effectively complemented by a redundant gene activity. Given the number of closely related homeobox genes that are expressed in the heart (and the rate at which new genes are being discovered), this is very likely to be the case for at least some homeobox gene activities. At present little is known of the precise mechanism of action of homeobox genes in embryonic development. This statement applies to homeobox genes in general, not just to genes involved in cardiovascular development. There is a popular view that homeobox genes are master regulators that control expression of a large number of downstream genes. In at least some cases, e.g., the eyeless gene of Drosophila (Holder et al., 1995), homeobox genes appear to be capable of activating and maintaining a very complex developmental program. Significantly, the eyeless gene is able to initiate eye development at numerous ectopic locations. Increasing evidence, however, suggests that genes of this type may be rather rare. Certainly there is no evidence to date that any of the homeobox genes expressed in the heart are able to initiate the complete heart development pathway. This is probably best understood in the case of the tinman gene in Drosophila, which, although absolutely required for heart development, is not capable of initiating the cardiac development pathway in ectopic locations (Bodmer, 1993). This conclusion is supported by studies of the vertebrate tinman-related gene Nkx2-5. Gene ablation studies show that Nkx2-5 is essential for correct cardiac development (Lyons et al., 1995) but is not able to initiate the regulatory pathway leading to cardiac development when expressed ectopically (Cleaver et al., 1996; Chen and Fishman, 1996). If most homeodomain proteins are not direct regulators of a differentiation pathway, what is their role during organogenesis? The cardiovascular homeobox gene about which most is known at the mechanistic level is gax (Smith et al., 1997). A number of experiments indicate that the Gax protein is involved in the regulation of cell proliferation and that it interacts with components of the cell cycle regulation machinery. Indeed, over recent years, the idea that at least some homeobox genes play their role in organogenesis through regulation of proliferation has been developed in some detail by Duboule (1995). Further evidence that this mechanism of homeobox activity is important, especially during organogenesis, comes from studies of the Hox11 homeobox gene, which is absolutely required for development of the spleen in mouse (Roberts et al., 1994). Studies indicate that Hox11 is able to interact with at least two different protein phosphatases, PP2A and PP1, which in turn, are involved in cell cycle regulation (Kawabe et al., 1997). It is quite clear that research in future years will need to focus on the precise mode of action of the different homeodomain proteins if we are to understand their role in the development of the cardiovascular system.

Animals↗
PubMed1997

Retinoic acid can block differentiation of the myocardium after heart specification.

While a number of transcription factors that are likely to play a role in cardiac differentiation have recently been described, the signals that lead to the expression of these factors remains poorly understood. Here we report that exposure of Xenopus embryos to continuous low levels of all-trans retinoic acid (RA), starting at the time of neural fold closure, blocks expression of myocardial differentiation markers. The development of the remainder of the embryo is relatively normal, suggesting that retinoic acid can act rather specifically on myocardial precursors. Indeed, the pattern of endocardial gene expression appears to remain unaffected by RA treatment. Although RA blocks myocardial gene expression, a superficially normal heart tube forms. The heart tube, however, fails to loop during subsequent development and never forms beating tissue. The effect of RA treatment on expression of myocardial genes is developmental stage dependent, since no influence is observed after myocardial differentiation has commenced. These data indicate that a vital component of the myocardial determination pathway is sensitive to retinoid signaling.

Animals↗
PubMed1997

Remarkable sequence conservation of transcripts encoding amphibian and mammalian homologues of quaking, a KH domain RNA-binding protein.

Mutations in the mouse quaking locus can result in two different types of developmental phenotypes: (1) a deficiency of myelin in the central nervous system that is accompanied by a characteristic tremor, or (2) embryonic lethality around day 9 of gestation. A quaking candidate gene (qkI) that encodes a KH motif protein has recently been identified. We have isolated and characterized cDNAs encoding the Xenopus quaking homologue (Xqua) and also assembled an almost complete human quaking sequence from expressed sequence tags. Sequence comparisons show that the amphibian and mammalian quaking transcripts exhibit striking conservation, both within the coding region and, unexpectedly, in the 3' UTR. Two Xqua transcripts 5 kb and 5.5 kb in length are differentially expressed in the Xenopus embryo, with the 5 kb transcript being detected as early as the gastrula stage of development. Using an in vitro assay, we have demonstrated RNA-binding activity for quaking protein encoded by the 5 kb transcript. Overall, the high sequence conservation of quaking sequences suggests an important conserved function in vertebrate development, probably in the regulation of RNA metabolism.

Amino Acid Sequence↗
PubMed1996

Overexpression of the tinman-related genes XNkx-2.5 and XNkx-2.3 in Xenopus embryos results in myocardial hyperplasia.

Drosophila tinman is an NK-class homeobox gene required for formation of the dorsal vessel, the insect equivalent of the vertebrate heart. Vertebrate sequences related to tinman, such as mouse Nkx-2.5, chicken cNkx-2.5, Xenopus XNkx-2.5 and XNkx-2.3 are expressed in cardiac precursors and in tissues involved in induction of cardiac mesoderm. Mice which lack a functional Nkx-2.5 gene die due to cardiac defects. To determine the role of tinman-related sequences in heart development, we have overexpressed both XNkx-2.3 and XNkx-2.5 in Xenopus laevis embryos. The resulting embryos are morphologically normal except that they have enlarged hearts. The enlarged heart phenotype is due to a thickening of the myocardium caused by an increase in the overall number of myocardial cells (hyperplasia). Neither ectopic nor precocious expression of cardiac differentiation markers is detectable in overexpressing embryos. These results suggest that both XNkx-2.3 and XNkx-2.5 are functional homologues of tinman, responsible for maintenance of the heart field.

Animals↗
PubMed1994

Cardiac troponin I is a heart-specific marker in the Xenopus embryo: expression during abnormal heart morphogenesis.

Cardiac troponin I (troponin Ic) expression is restricted to the heart at all stages of Xenopus development. Whole-mount in situ hybridization and Northern blot analysis indicates that troponin Ic is first expressed in tailbud embryos (stage 28) about the time of the first cytological heart differentiation and about 24 hr before beating tissue is observed. We have used this marker to examine abnormal heart morphogenesis in embryos treated with retinoic acid and lithium. When retinoic acid is administered to embryos prior to heart specification, heart tissue is reduced and often completely ablated. When embryos are treated after heart specification, but before the heart primordium migrates to the ventral midline, the migration is unaffected but smaller, abnormal hearts result. Lithium treatment of cleavage stage embryos causes an increase in heart tissue. In severely dorsalized embryos, heart tissue can be found around the entire embryo with the exception of a small gap at the most dorsal point. This gap indicates that migration of the heart to the ventral midline does not occur in these embryos. Later in development, a centrally located, beating heart is observed in dorsalized embryos. The timing of its appearance suggests that it is formed by movements normally associated with heart morphogenesis rather than migration.

Animals↗
PubMed1994

Cholera diffusion in Russia, 1823-1923.

All six cholera pandemics of the 19th and early 20th centuries struck Russia, causing millions of deaths. Cholera entered Russia from the south, with the Volga river system being a common and efficient route into the heart of the country. Diffusion was predominantly linear, along the navigable rivers and later, along the railroads. In contrast to Pyle's findings for the U.S.A., urban hierarchical diffusion was of only local significance in Russia.

Cholera↗
PubMed1992

Yellow fever epidemics and mortality in the United States, 1693-1905.

Yellow fever epidemics struck the United States repeatedly in the 18th and 19th centuries. The disease was not indigenous; epidemics were imported by ship from the Caribbean. Prior to 1822, yellow fever attacked cities as far north as Boston, but after 1822 it was restricted to the south. Port cities were the primary targets, but the disease occasionally spread up the Mississippi River system in the 1800s. New Orleans, Mobile, Savannah, and Charleston were major targets; Memphis suffered terribly in 1878. Yellow fever epidemics caused terror, economic disruption, and some 100,000-150,000 deaths. Recent white immigrants to southern port cities were the most vulnerable; local whites and blacks enjoyed considerable resistance.

Disease Outbreaks↗
PubMed1985

Pandemic and epidemic influenza, 1830-1848.

Four major influenza epidemics were recorded between 1830 and 1848. The 1830-1831 epidemic may have originated in China; then and in 1833 influenza advanced westward out of Russia into Europe. In 1836-1837, influenza diffusion was largely north to south, and in 1847-1848 the disease swept through the Mediterranean to southern France and thence elsewhere in Western Europe. Each of the four epidemics spread rapidly and caused very high morbidity rates. Although case-mortality rates were always low, each epidemic killed thousands of people, with most deaths being among the elderly. Many previous writers have described all four outbreaks as pandemics, but true pandemics, presumably caused by major new viral types, are clearly identifiable only in 1830-1831 and 1833. The status of the 1836-1837 outbreak is unclear, but there was no pandemic in 1847-1848.

Disease Outbreaks↗
PubMed1983

The diffusion of influenza in sub-Saharan Africa during the 1918-1919 pandemic.

The focus of this study is the spread of influenza in Africa south of the Sahara during the pandemic of 1918-1919. Most known types of diffusion pattern, i.e. radial, wave-like and linear, have been identified; however, the disease spread to rapidly that four particularly devastating linear patterns stand out. One of the most incredible aspects of the regularity in epidemic velocity along these pathways was that the colonial transportation network was of fairly recent origin. Given modern transportation linkages, the ever-present danger of the resurgence of the agent or agents that caused the pandemic could result in a much greater disaster in Africa and other Third World areas if unabated by effective inoculation programs.

Africa, Eastern↗