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Results for “Wnt4 Protein”

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At least 19 recordsLinked to original sources
PubMed2006

Differential expression of WNT4 in testicular and ovarian development in a marsupial.

BACKGROUND: WNT4 is a key regulator of gonadal differentiation in humans and mice, playing a pivotal role in early embryogenesis. Using a marsupial, the tammar wallaby, in which most gonadal differentiation occurs after birth whilst the young is in the pouch, we show by quantitative PCR during early testicular and ovarian development that WNT4 is differentially expressed in gonads. RESULTS: Before birth, WNT4 mRNA expression was similar in indifferent gonads of both sexes. After birth, in females WNT4 mRNA dramatically increased during ovarian differentiation, reaching a peak by day 9-13 post partum (pp) when the ovarian cortex and medulla are first distinguishable. WNT4 protein was localised in the ovarian cortex and at the medullary boundary. WNT4 mRNA then steadily decreased to day 49, by which time all the female germ cells have entered meiotic arrest. In males, WNT4 mRNA was down-regulated in testes immediately after birth, coincident with the time that seminiferous cords normally form, and rose gradually after day 8. By day 49, when testicular androgen production normally declines, WNT4 protein was restricted to the Leydig cells. CONCLUSION: This is the first localisation of WNT4 protein in developing gonads and is consistent with a role for WNT4 in steroidogenesis. Our data provide strong support for the suggestion that WNT4 not only functions as an anti-testis gene during early development, but is also necessary for later ovarian and testicular function.

Amino Acid Sequence↗
PubMed2003

Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling.

Commissural neurons in the mammalian dorsal spinal cord send axons ventrally toward the floor plate, where they cross the midline and turn anteriorly toward the brain; a gradient of chemoattractant(s) inside the spinal cord controls this turning. In rodents, several Wnt proteins stimulate the extension of commissural axons after midline crossing (postcrossing). We found that Wnt4 messenger RNA is expressed in a decreasing anterior-to-posterior gradient in the floor plate, and that a directed source of Wnt4 protein attracted postcrossing commissural axons. Commissural axons in mice lacking the Wnt receptor Frizzled3 displayed anterior-posterior guidance defects after midline crossing. Thus, Wnt-Frizzled signaling guides commissural axons along the anterior-posterior axis of the spinal cord.

Animals↗
PubMed1996

Gene targeting in kidney development.

Cancer and development are conceptually related because tumor formation in many cases results from the aberrant expression of a developmental program. This is certainly true of Wilms' tumors, which display a range of phenotypes resembling various stages of kidney development. WT1 has been identified as a tumor suppressor gene involved in a subset of Wilms' tumors. Gene targeting of the WT1 gene demonstrated the requirement for this gene product during early urogenital development. Several other genes, including Wnt-4, c-ret, ld and lim 1, have been shown by gene targeting to also be involved in early kidney development. This review discusses gene targeting as an approach to the study of development and reviews the phenotypes of these and other genes involved in kidney organogenesis.

Animals↗
PubMed1998

sFRP-2 is a target of the Wnt-4 signaling pathway in the developing metanephric kidney.

Members of the Wnt family of secreted glycoproteins act as short-range signaling molecules in vertebrate embryogenesis. Previous work has shown that Wnt-4 is required for kidney development. Mice lacking functional Wnt-4 fail to form pretubular cell aggregates. Wnt-4 acts as an autoinducer of the mesenchymal to epithelial transition underlying nephron development. We have identified a member of the gene family encoding secreted frizzled related proteins (sFRP), putative Wnt antagonists, that shows overlapping expression with Wnt-4 in aggregating mesenchyme and simple epithelial bodies during metanephric development. sFRP-2 expression is absent in metanephric mesenchyme of kidneys mutant for Wnt-4 and is coinduced with Wnt-4 in isolated metanephric mesenchyme by cells expressing Wnt-4. The cysteine-rich domain of sFRP-2 binds to Wnt-4 as shown by coimmunoprecipitation experiments. Hence, sFRP-2 is a target of the Wnt-4 signaling pathway in the metanephric kidney and may modulate Wnt-4 signaling. sFRP-2 expression is highly dynamic and specific during other aspects of embryogenesis. sFRP-2 is expressed in subpopulations of ependymal cells in spinal cord and brain, in the developing eye, in limb bud mesenchyme, in the heart, and strongly in skeletogenic condensations of facial bones, suggesting widespread interaction with other members of the Wnt gene family during embryogenesis.

Animals↗
PubMed1999

Perturbation of RET signaling in the embryonic kidney.

We have used a RET-Ig fusion protein to disrupt signaling in the rat embryonic kidney development pathway. Treatment of embryonic kidney organ cultures with RET-Ig results in a decrease in branching of the ureteric bud and a down regulation in expression of the Wnt-11, Wnt-4, and ld genes. These data suggest that Wnt-11, Wnt-4, and ld function downstream of RET signaling in normal development. Expression of BMP-7, shh, and ptc were uneffected by RET-Ig treatment, implying that these genes are regulated independently of ret. We have also performed immunohistochemistry with a GFR alpha-1 specific polyclonal antisera to localize GFR alpha-1 protein expression in the developing kidney.

Animals↗
PubMed2002

Wnt-1 and Wnt-4 regulate thymic cellularity.

Thymic primordium, formed by cells derived from the endoderm, the ectoderm and the neural crest-derived mesenchyme, receive fetal liver derived lymphoid precursors. Reciprocal cell-cell interactions between thymic stromal cells and lymphoid precursors are critical in the expansion and maturation of thymocytes. Transcription factor TCF-1 is critical for the expansion of thymocytes because deletion of TCF-1 results in a significant decrease in the number of thymocytes without affecting the developmental pattern. In this report we show that Wnt-1 and Wnt-4 are expressed in the thymus and the deletion of Wnt-1 or Wnt-4 result in a substantial decrease in the number of thymocytes without affecting the pattern of maturation. Wnt-1 and Wnt-4 both regulate developing thymocytes because a double deficiency results in a significantly greater decrease of immature and mature thymocytes compared to deficiency in either Wnt-1 or Wnt-4.

Amphibian Proteins↗
PubMed2007

Determination and stability of sex.

How is the embryonic bipotential gonad regulated to produce either an ovary or a testis? In males, transient early activation of the Y chromosome Sry gene makes both germ cells and soma male. However, in females, available evidence suggests that the process of ovary sex determination may take place independently in the germline and somatic lineages. In addition, in contrast to testis, in ovary somatic cells, female-to-male gonadal sex reversal can occur at times throughout ovary development and maturation. We suggest that a single gene pathway, likely hinging on the Foxl2 transcription factor, both initiates and maintains sex differentiation in somatic cells of the mammalian ovary.

Animals↗
PubMed2001

Induction of ureter branching as a response to Wnt-2b signaling during early kidney organogenesis.

Epithelial-mesenchymal tissue interactions play a central role in vertebrate organogenesis, but the molecular mediators and mechanisms of these morphogenetic interactions are still not well characterized. We report here on the expression pattern of Wnt-2b during mouse organogenesis and on tests of its function in epithelial- mesenchymal interactions during kidney development. Wnt-2b is expressed in numerous developing organs in the mouse embryo, including the kidney, lung, salivary gland, gut, pancreas, adrenal gland, and genital tubercle. Additional sites of expression include the branchial arches and craniofacial placodes such as the eye and ear. The data suggest that the expression of Wnt-2b is associated with organs regulated by epithelial-mesenchymal interactions. It is typically localized in the capsular epithelium or peripheral mesenchymal cells of organ rudiments, e.g., the perinephric mesenchymal cells in the region of the presumptive renal stroma in the developing kidney at E11.5. Functional studies of the kidney demonstrate that cells expressing Wnt-2b are not capable of inducing tubule formation but instead stimulate ureter development. Incubation of isolated ureteric buds on such cells supports bud growth and branching. In addition, recombination of Wnt-2b-pretreated ureteric bud tissue with isolated nephrogenic mesenchyme results in a recovery of organogenesis and the expression of epithelial genes within the reconstituted organ explant. Lithium, a known activator of Wnt signaling (Hedgepeth et al. [1997] Dev Biol 185:82-91), is also sufficient to promote ureter branching in the reconstituted kidney in a comparable manner to Wnt-2b signaling, whereas Wnt-4, which induces tubules, neither supports the growth of a ureteric bud nor leads to reconstitution of the ureteric bud with the kidney mesenchyme. We conclude that Wnt-2b may act in the mouse kidney as an early mesenchymal signal controlling morphogenesis of epithelial tissue, and that the Wnt pathway may regulate ureter branching directly. In addition, Wnt signals in the kidney differ qualitatively and are specific to either the epithelial ureteric bud or the kidney mesenchyme.

3T3 Cells↗
PubMed2001

Wnts and the female reproductive system.

Wnts are intercellular growth and differentiation factors that regulate several key developmental steps, such as gastrulation, neurulation, and organogenesis, including the development of the midbrain, central nervous system, kidney, and limbs. Wnts are also needed for a normal development of the reproductive system. Deficiency of Wnt-4, -5a, and -7a, for example, results in sex reversal, infertility, and/or malformation of the internal and external genitals. Here we focus on the importance of Wnts in the female reproductive system.

Animals↗
PubMed1994

Regional expression of the Cwnt-4 gene in developing chick central nervous system in relationship to the diencephalic neuromere D2 and a dorsal domain of the spinal cord.

Members of the Wnt gene family code for cysteine-rich, secreted proteins, which are differentially expressed in the developing brain and possibly act as an intercellular signaling molecule. A Wnt gene, e.g., Wnt-1 is known to be essential for specification of the midbrain cell fate. Since other members of the Wnt genes are likely to be also involved in development of the brain, we searched chick Wnt members expressing in specific domains of the brain. We found several novel Wnt members expressing specifically in the central nervous system of chick embryos. One of the genes was intensely expressed in a segment of the diencephalon at stages 14 and 20 and in a dorsal region of the spinal cord at stage 20. Although the expression patterns differ from those of mouse or Xenopus Wnt-4, the gene is highly homologous to the mouse or frog Wnt-4. Thus, we designated the gene as Cwnt-4 (chick Wnt-4). Our results suggested that Cwnt-4 is involved in segmentation of the forebrain into the neuromere D2 and in differentiation of the dorsal region of the spinal cord.

Amino Acid Sequence↗
PubMed1995

Wnt-4 expression induces a pregnancy-like growth pattern in reconstituted mammary glands in virgin mice.

Expression of Wnt-4, a member of the Wnt gene family, is induced during early pregnancy in the mouse mammary gland. To investigate the function of Wnt-4, we used a recombinant retrovirus to constitutively express the gene in transplanted mammary epithelium grown in virgin animals. In fully grown glands, Wnt-4 expression resulted in ducts that were more highly branched than normal and caused some premature alveolar development. These changes resembled those seen during pregnancy, suggesting that endogenous Wnt-4 expression may regulate epithelial branching in early pregnancy. The modified growth pattern induced by Wnt-4 expression was similar to that induced by Wnt-1, one of the members of the Wnt gene family activated by mouse mammary tumour virus. As Wnt-1 is not normally expressed in the mammary gland, it may exert its effect on the mammary gland by activating a developmental pathway normally regulated by Wnt-4.

Animals↗
PubMed2001

DWnt4 and wingless elicit similar cellular responses during imaginal development.

Wnt genes encode evolutionarily conserved secreted proteins that provide critical functions during development. Although Wnt proteins share highly conserved features, they also show sequence divergence, which almost certainly contributes to the variety of their signaling activities. We previously reported that DWnt4 and wingless (wg), two divergent clustered Wnt genes, can have either antagonist or distinct functions during Drosophila embryogenesis. Here we provide evidence that both genes can elicit similar cellular responses during imaginal development. Ectopic expression of DWnt4 along the anterior/posterior (A/P) boundary of imaginal discs alters morphogenesis of adult appendages. In the wing disc, DWnt4 phenocopies ectopic Wg activity by inducing notum to wing transformation, suggesting similar signaling capabilities of both molecules. In support of this, we demonstrate that DWnt4 can rescue wg loss-of-function phenotypes in the antenna and haltere and is able to substitute for Wg in wing field specification. We also show that both genes are transcribed in overlapping domains in imaginal discs, suggesting that DWnt4 may cooperate with wg during limb patterning.

Animals↗
PubMed2001

Wnt and BMP signaling govern lineage segregation of melanocytes in the avian embryo.

Recent studies show that specification of some neural crest lineages occurs prior to or at the time of migration from the neural tube. We investigated what signaling events establish the melanocyte lineage, which has been shown to migrate from the trunk neural tube after the neuronal and glial lineages. Using in situ hybridization, we find that, although Wnts are expressed in the dorsal neural tube throughout the time when neural crest cells are migrating, the Wnt inhibitor cfrzb-1 is expressed in the neuronal and glial precursors and not in melanoblasts. This expression pattern suggests that Wnt signaling may be involved in specifying the melanocyte lineage. We further report that Wnt-3a-conditioned medium dramatically increases the number of pigment cells in quail neural crest cultures while decreasing the number of neurons and glial cells, without affecting proliferation. Conversely, BMP-4 is expressed in the dorsal neural tube throughout the time when neural crest cells are migrating, but is decreased coincident with the timing of melanoblast migration. This expression pattern suggests that BMP signaling may be involved in neural and glial cell differentiation or repression of melanogenesis. Purified BMP-4 reduces the number of pigment cells in culture while increasing the number of neurons and glial cells, also without affecting proliferation. Our data suggest that Wnt signaling specifies melanocytes at the expense of the neuronal and glial lineages, and further, that Wnt and BMP signaling have antagonistic functions in the specification of the trunk neural crest.

Animals↗
PubMed1998

Characterization of Wnt gene expression in murine skin: possible involvement of epidermis-derived Wnt-4 in cutaneous epithelial-mesenchymal interactions.

Wnt glycoproteins mediate short range intracellular communication that facilitates morphogenesis and, in some settings, promotes tumor formation. Although the involvement of the Drosophila homolog wingless in ectodermal patterning is well established, the role that Wnt genes play in mammalian skin biology is not defined. We detected Wnt-4 and Wnt-10b mRNA in adult murine epidermis using degenerate primers and reverse transcriptase PCR, and confirmed expression by RNase protection. Normal murine keratinocytes and a melanocyte cell line (melan-A) propagated in vitro also contained Wnt-4 mRNA, whereas dermal fibroblasts and Langerhans cell-like dendritic cells did not. Because Wnt-4 mRNA was more abundant than Wnt-10b mRNA in epidermis and Wnt-10b trancripts were not detected in cells propagated in vitro, additional studies emphasized Wnt-4 exclusively. Wnt-4 mRNA levels were increased in cultured keratinocytes as they approached confluence and were strikingly downregulated by mitogenic growth factors. Although Wnt-4 mRNA levels were not modulated during calcium-induced keratinocyte differentiation in vitro, assessment of Wnt-4 transcripts in keratinocyte cell lines suggested that loss of Wnt-4 gene expression was associated with a less differentiated, more malignant, phenotype. Despite this, epidermal abnormalities were not identified in newborn Wnt-4 null (-/-) skin, or in full-thickness -/- skin that was engrafted to nude or athymic mice and allowed to mature for as long as 3 months. However, histologic examination of newborn Wnt-4 null skin did reveal fibroplasia involving the dermis with increased accumulation of type I collagen fibrils. These results indicate that several Wnt genes are expressed in adult murine epidermis and suggest that Wnt-4 proteins may be involved in epidermal-dermal interactions in mammalian skin.

Animals↗
PubMed2000

DWnt-4 and Wingless have distinct activities in the Drosophila dorsal epidermis.

Wnt genes are often expressed in overlapping patterns, where they affect a wide array of developmental processes. To address the way in which various Wnt signals elicit distinct effects we compared the activities of two Wnt genes in Drosophila, DWnt-4, and wingless. We show that these Wnt signals produce distinct responses in cells of the dorsal embryonic epidermis. Whereas wingless acts independently of hedgehog signaling in these cells, we show that DWnt-4 requires Hh to elicit its effects. We also show that expression of Wg signal transduction components does not mimic expression of DWnt-4, suggesting that DWnt-4 signaling proceeds through a distinct pathway. The dorsal epidermis may therefore be useful in the identification of novel Wnt signaling components.

Animals↗
PubMed2006

Pax3 and Pax7 expression and regulation in the avian embryo.

Satellite cells are essential for postnatal growth and repair of skeletal muscle. The paired-box transcription factors Pax3 and Pax7 are expressed in emerging muscle precursors. Recent studies have traced the origin of satellite cells to the embryonic dermomyotome, however, their developmental regulation throughout embryogenesis remains unclear. We show the overlying surface ectoderm and lateral plate are essential for Pax3 expression, and that the overlying surface ectoderm and neural tube are necessary for Pax7 expression within the dorsal somite. Furthermore we show that the notochord acts to down regulate the expression of both genes. Moreover, we identify diffusible factors within these tissues that act to maintain expression of Pax3 ( + ) and Pax7 (+) muscle precursors. We show that Wnt1, 3a, 4 and 6 proteins are able to up regulate and expand the expression of Pax3 and Pax7 within the dorsal somite. Finally, we show that Wnt6 can mimic the effect of the dorsal ectoderm to maintain Pax3 and Pax7 expression.

Animals↗