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P A Krieg

Publications and source records attributed to P A Krieg.

At least 19 recordsLinked to original sources
PubMed2001

Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor.

Serum response factor (SRF) regulates transcription of numerous muscle and growth factor-inducible genes. Because SRF is not muscle specific, it has been postulated to activate muscle genes by recruiting myogenic accessory factors. Using a bioinformatics-based screen for unknown cardiac-specific genes, we identified a novel and highly potent transcription factor, named myocardin, that is expressed in cardiac and smooth muscle cells. Myocardin belongs to the SAP domain family of nuclear proteins and activates cardiac muscle promoters by associating with SRF. Expression of a dominant negative mutant of myocardin in Xenopus embryos interferes with myocardial cell differentiation. Myocardin is the founding member of a class of muscle transcription factors and provides a mechanism whereby SRF can convey myogenic activity to cardiac muscle genes.

Amino Acid Sequence↗
PubMed2001

Notochord patterning of the endoderm.

Endodermally derived organs of the gastrointestinal and respiratory system form at distinct anterioposterior and dorsoventral locations along the vertebrate body axis. This stereotyped program of organ formation depends on the correct patterning of the endodermal epithelium so that organ differentiation and morphogenesis occur at appropriate positions along the gut tube. Whereas some initial patterning of the endoderm is known to occur early, during germ-layer formation and gastrulation, later signaling events, originating from a number of adjacent tissue layers, are essential for the development of endodermal organs. Previous studies have shown that signals arising from the notochord are important for patterning of the ectodermally derived floor plate of the neural tube and the mesodermally derived somites. This review will discuss recent evidence indicating that signals arising from the notochord also play a role in regulating endoderm development.

Body Patterning↗
PubMed2001

Developmental expression of the Xenopus Iroquois-family homeobox genes, Irx4 and Irx5.

We have isolated and characterized the developmental expression of the Xenopus Iroquois 4 (Irx4) and Iroquois 5 (Irx5) homeodomain transcription factors. Irx4 is expressed in a subset of cells in the neural retina and the developing hindbrain and also, specifically, in the ventricle of the heart. Xenopus Irx5 is expressed in the developing midbrain, hindbrain, neural tube, and also in the retina.

Amino Acid Sequence↗
PubMed2000

Transient cardiac expression of the tinman-family homeobox gene, XNkx2-10.

In Drosophila, the tinman homeobox gene is absolutely required for heart development. In the vertebrates, a small family of tinman-related genes, the cardiac NK-2 genes, appear to play a similar role in the formation of the vertebrate heart. However, targeted gene ablation of one of these genes, Nkx2-5, results in defects in only the late stages of cardiac development suggesting the presence of a rescuing gene function early in development. Here, we report the characterization of a novel tinman-related gene, XNkx2-10, which is expressed during early heart development in Xenopus. Using in vitro assays, we show that XNkx2-10 is capable of transactivating expression from promoters previously shown to be activated by other tinman-related genes, including Nkx2-5. Furthermore, Xenopus Nkx2-10 can synergize with the GATA-4 and SRF transcription factors to activate reporter gene expression.

Amino Acid Sequence↗
PubMed2000

Expression of atrial natriuretic factor (ANF) during Xenopus cardiac development.

We have isolated the Xenopus orthologue of the atrial natriuretic factor (ANF) gene. Characterization of embryonic expression indicates that the ANF gene is initially expressed throughout the developing myocardium at the late heart tube stage (about stage 32). This is in contrast to all previously characterized Xenopus cardiac differentiation markers that are first expressed in the cardiogenic plate at approximately stage 27. ANF expression becomes restricted exclusively to the atrium at about stage 47, long after the commencement of beating and the original formation of the atrial and ventricular compartments, but shortly after septation of the single atrium into two distinct atria.

Amino Acid Sequence↗
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

Gdf16, a novel member of the growth/differentiation factor subgroup of the TGF-beta superfamily, is expressed in the hindbrain and epibranchial placodes.

We have isolated and characterized the developmental expression of Xenopus gdf16, a novel member of the growth/differentiation factor (gdf) gene family. The gdf16 gene encodes a pre-proprotein of 413 amino acids and a mature peptide of 122 amino acids. Gdf16 is most closely related to the zebrafish genes dynamo and radar, but exhibits a completely different expression pattern. Gene expression is detected at early tailbud (stage 25) in the first two epibranchial placodes and in a hindbrain-specific domain. As development proceeds, the gene is expressed in all the epibranchial placodes, the hindbrain, and the diencephalon.

Amino Acid Sequence↗
PubMed2000

Developmental expression of the Xenopus Nkx2-1 and Nkx2-4 genes.

The homeodomain transcription factor Nkx2-1 (TTF-1) plays an essential role in the development of the thyroid, lung and ventral forebrain. We report the cloning and developmental expression patterns of two Xenopus NK-2 genes, Nkx2-1 and Nkx2-4, that are closely related to Nkx2-1. These genes show readily distinguishable expression patterns during development. Similar to its orthologues in chicken and mouse, the Xenopus Nkx2-1 gene is expressed in the developing thyroid, lung, and ventral forebrain. In contrast, expression of Nkx2-4 is specifically localized to the ventral diencephalon.

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↗
PubMed2000

Endoderm patterning by the notochord: development of the hypochord in Xenopus.

The patterning and differentiation of the vertebrate endoderm requires signaling from adjacent tissues. In this report, we demonstrate that signals from the notochord are critical for the development of the hypochord, which is a transient, endodermally derived structure that lies immediately ventral to the notochord in the amphibian and fish embryo. It appears likely that the hypochord is required for the formation of the dorsal aorta in these organisms. We show that removal of the notochord during early neurulation leads to the complete failure of hypochord development and to the elimination of expression of the hypochord marker, VEGF. Removal of the notochord during late neurulation, however, does not interfere with hypochord formation. These results suggest that signals arising in the notochord instruct cells in the underlying endoderm to take on a hypochord fate during early neural stages, and that the hypochord does not depend on further notochord signals for maintenance. In reciprocal experiments, when the endoderm receives excess notochord signaling, a significantly enlarged hypochord develops. Overall, these results demonstrate that, in addition to patterning neural and mesodermal tissues, the notochord plays an important role in patterning of the endoderm.

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↗
PubMed1999

Alternative splicing and embryonic expression of the Xenopus mad4 bHLH gene.

The cell proliferative activity of the Myc family of basic helix-loop-helix/leucine zipper (bHLHZip) transcription factors is dependent upon binding to the ubiquitous Max protein. In the absence of heterodimerization with Max, Myc protein is unable to efficiently bind to DNA and activate transcription. Members of the Mad family of transcription factors are thought to modulate the cell proliferative effects of the c-myc proto-oncogene by binding to Max, directly competing with the Myc protein for both heterodimerization and DNA binding. Consistent with a role in down-regulating cell division, the murine mad genes are expressed in embryonic tissues undergoing differentiation, often during or shortly after the down-regulation of myc gene expression. Here, we report the isolation and characterization of the first Xenopus mad family member, Xmad4. Maternal Xmad4 transcripts are present at high levels in the oocyte and in the cleavage stage embryo, but almost disappear by the neurula stage. Zygotic expression of the Xmad4 gene is initiated in the epidermis of the late neurula stage, and shortly thereafter, Xmad4 is transiently detectable in the cement and hatching glands. At later stages, expression is also observed in the developing pronephros and liver. Unlike the murine mad4 gene, we find that multiple Xmad4 splice variants exist in Xenopus and that these variants are differentially expressed in both the embryo and the adult. Despite the demonstrated antagonistic role of Mad proteins in the regulation of Myc activity, we show that the over-expression of Xmad4 in the cleavage-stage embryo has no detectable phenotypic effect, suggesting that Myc function is dispensable during early embryonic development.

Alternative Splicing↗
PubMed1999

The Xenopus bagpipe-related homeobox gene zampogna is expressed in the pharyngeal endoderm and the visceral musculature of the midgut.

In Drosophila, the bagpipe homeobox gene is expressed in a subset of dorsal mesodermal cells and in the absence of bagpipe gene function, development of the visceral musculature is disrupted. In Xenopus, one bagpipe-related gene, Xbagpipe (Xbap) has previously been described. Here we report the isolation of a second Xenopus homologue named zampogna (zax). zax is transcribed within the muscular layer of the forming midgut as well as in the embryonic head, where zax transcripts mark both the pharyngeal endoderm and the future infrarostral cartilage.

Amino Acid Sequence↗
PubMed1999

The RNA-binding protein gene, hermes, is expressed at high levels in the developing heart.

In a screen for novel sequences expressed during embryonic heart development we have isolated a gene which encodes a putative RNA-binding protein. This protein is a member of one of the largest families of RNA-binding proteins, the RRM (RNA Recognition Motif) family. The gene has been named hermes (for HEart, RRM Expressed Sequence). The hermes protein is 197-amino acids long and contains a single RRM domain. In situ hybridization analysis indicates that hermes is expressed at highest levels in the myocardium of the heart and to a lesser extent in the ganglion layer of the retina, the pronephros and epiphysis. Expression of hermes in each of these tissues begins at approximately the time of differentiation and is maintained throughout development. Analysis of the RNA expression of the hermes orthologues from chicken and mouse reveals that, like Xenopus, the most prominent tissue of expression is the developing heart. The sequence and expression pattern of hermes suggests a role in post-transcriptional regulation of heart development.

Amino Acid Sequence↗