References of "Balling, Rudi 50000566"
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See detailA locus for radiation-induced gastroschisis on mouse Chromosome 7.
Hillebrandt, S.; Streffer, C.; Montagutelli, X. et al

in Mammalian Genome (1998), 9(12), 995-7

Gastroschisis (abdominal wall defects) occurs with a high frequency in the mouse inbred strain HLG compared with C57BL/6J mice. The risk of gastroschisis increases significantly after exposure to ... [more ▼]

Gastroschisis (abdominal wall defects) occurs with a high frequency in the mouse inbred strain HLG compared with C57BL/6J mice. The risk of gastroschisis increases significantly after exposure to irradiation with X-rays during preimplantation development and follows a recessive mode of inheritance for the HLG susceptibility alleles. We have used a backcross strategy and genome-wide microsatellite typing to chromosomally map this trait. A suggestive linkage for a locus responsible for radiation-induced gastroschisis (Rigs1) was found in a region of mouse Chromosome 7. [less ▲]

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See detailPax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities.
Peters, H.; Neubuser, A.; Kratochwil, K. et al

in Genes and Development (1998), 12(17), 2735-47

Pax genes have been shown to play important roles in mammalian development and organogenesis. Pax9, a member of this transcription factor family, is expressed in somites, pharyngeal pouches, mesenchyme ... [more ▼]

Pax genes have been shown to play important roles in mammalian development and organogenesis. Pax9, a member of this transcription factor family, is expressed in somites, pharyngeal pouches, mesenchyme involved in craniofacial, tooth, and limb development, as well as other sites during mouse embryogenesis. To analyze its function in vivo, we generated Pax9 deficient mice and show that Pax9 is essential for the development of a variety of organs and skeletal elements. Homozygous Pax9-mutant mice die shortly after birth, most likely as a consequence of a cleft secondary palate. They lack a thymus, parathyroid glands, and ultimobranchial bodies, organs which are derived from the pharyngeal pouches. In all limbs, a supernumerary preaxial digit is formed, but the flexor of the hindlimb toes is missing. Furthermore, craniofacial and visceral skeletogenesis is disturbed, and all teeth are absent. In Pax9-deficient embryos tooth development is arrested at the bud stage. At this stage, Pax9 is required for the mesenchymal expression of Bmp4, Msx1, and Lef1, suggesting a role for Pax9 in the establishment of the inductive capacity of the tooth mesenchyme. In summary, our analysis shows that Pax9 is a key regulator during the development of a wide range of organ primordia. [less ▲]

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See detailWe need more mutants: Plans for a large scale ENU mouse mutagenesis screen
Balling, Rudi UL; Hrabe de Angelis, M; Schughart, K et al

in OECD Economics Department Working Papers (1998), (98), 103-111

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See detailDie Maus
Balling, Rudi UL

in Seyffert (Ed.) Lehrbuch der Genetik (1998)

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See detailWhose law for sharing research tools?
Balling, Rudi UL

in Nature (1998), 396(6711), 509

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See detailTargeted disruption of Pax1 defines its null phenotype and proves haploinsufficiency.
Wilm, B.; Dahl, E.; Peters, H. et al

in Proceedings of the National Academy of Sciences of the United States of America (1998), 95(15), 8692-7

The murine paired box-containing gene Pax1 is required for normal development of the vertebral column, the sternum, and the scapula. Previous studies have shown that three natural Pax1 mouse mutants, the ... [more ▼]

The murine paired box-containing gene Pax1 is required for normal development of the vertebral column, the sternum, and the scapula. Previous studies have shown that three natural Pax1 mouse mutants, the undulated alleles, exhibit phenotypes of different severity in these skeletal elements. Nevertheless, these analyses have not clarified whether the semidominant Undulated short-tail (Uns) mutation, in which the complete Pax1 locus is deleted, represents a null allele. Moreover, the analyses of the classical undulated mutants did not allow a conclusion with respect to haploinsufficiency of Pax1. To address both questions we have created a Pax1 null allele in mice by gene targeting. Surprisingly, the phenotype of this defined mutation exhibits clear differences to that of Uns. This result strongly indicates the contribution of additional gene(s) to the Uns mutant phenotype. Furthermore, the phenotype of mice heterozygous for the null allele demonstrates that Pax1 is haploinsufficient in some though not all skeletal elements which express Pax1 during embryonic development. [less ▲]

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See detailSegment-specific expression of the gap junction gene connexin 31 during hindbrain development
Dahl, E; Willecke, K; Balling, Rudi UL

in Development Genes & Evolution (1997), (207), 359-361

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See detailTransgenic technology as a tool
Balling, Rudi UL

in P. Thorogood (edt.) Embryos, Genes and Birth (1997)

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See detailIsolation of the Pax9 cDNA from adult human esophagus.
Peters, H.; Schuster, G.; Neubuser, A. et al

in Mammalian Genome (1997), 8(1), 62-4

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See detailAntagonistic interactions between FGF and BMP signaling pathways: a mechanism for positioning the sites of tooth formation.
Neubuser, A.; Peters, H.; Balling, Rudi UL et al

in Cell (1997), 90(2), 247-55

Vertebrate organogenesis is initiated at sites that are often morphologically indistinguishable from the surrounding region. Here we have identified Pax9 as a marker for prospective tooth mesenchyme prior ... [more ▼]

Vertebrate organogenesis is initiated at sites that are often morphologically indistinguishable from the surrounding region. Here we have identified Pax9 as a marker for prospective tooth mesenchyme prior to the first morphological manifestation of odontogenesis. We provide evidence that the sites of Pax9 expression in the mandibular arch are positioned by the combined activity of two signals, one (FGF8) that induces Pax9 expression and the other (BMP2 and BMP4) that prevents this induction. Thus it appears that the position of the teeth is determined by a combination of two different types of signaling molecules produced in wide but overlapping domains rather than by a single localized inducer. We suggest that a similar mechanism may be used for specifying the sites of development of other organs. [less ▲]

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See detailPax genes and organogenesis.
Dahl, E.; Koseki, H.; Balling, Rudi UL

in BioEssays (1997), 19(9), 755-65

Pax genes are a family of developmental control genes that encode nuclear transcription factors. They are characterized by the presence of the paired domain, a conserved amino acid motif with DNA-binding ... [more ▼]

Pax genes are a family of developmental control genes that encode nuclear transcription factors. They are characterized by the presence of the paired domain, a conserved amino acid motif with DNA-binding activity. Originally, paired-box-containing genes were detected in Drosophila melanogaster, where they exert multiple functions during embryogenesis. In vertebrates, Pax genes are also involved in embryogenesis. Mutations in four out of nine characterized Pax genes have been associated with either congenital human diseases such as Waardenburg syndrome (PAX3), Aniridia (PAX6), Peter's anomaly (PAX6), renal coloboma syndrome (PAX2) or spontaneous mouse mutants (undulated (Pax1), Splotch (Pax3), Small eye (Pax6), Pax2(1)Neu), which all show defects in development. Recently, analysis of spontaneous and transgenic mouse mutants has revealed that vertebrate pax genes are key regulators during organogenesis of kidney, eye, ear, nose, limb muscles, vertebral column and brain. Like their Drosophila counterparts, vertebrate Pax genes are involved in pattern formation during embryogenesis, possibly by determining the time and place of organ initiation or morphogenesis. For most tissues, however, the nature of the primary developmental action of Pax transcription factors remains to be elucidated. One predominant theme is signal transduction during tissue interactions, which may lead to a position-specific regulation of cell proliferation. [less ▲]

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See detailThe Genetics of Vertebral Column Development
Peters, H; Neubüser, A; Wallin, J et al

in Thiel; Klug (Eds.) Methods in Developmental Toxicology (1997)

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See detailPAX genes and human neural tube defects: an amino acid substitution in PAX1 in a patient with spina bifida.
Hol, F. A.; Geurds, M. P.; Chatkupt, S. et al

in Journal of Medical Genetics (1996), 33(8), 655-60

From studies in the mouse and from the clinical and molecular analysis of patients with type 1 Waardenburg syndrome, particular members of the PAX gene family are suspected factors in the aetiology of ... [more ▼]

From studies in the mouse and from the clinical and molecular analysis of patients with type 1 Waardenburg syndrome, particular members of the PAX gene family are suspected factors in the aetiology of human neural tube defects (NTD). To investigate the role of PAX1, PAX3, PAX7, and PAX9, allelic association studies were performed in 79 sporadic and 38 familial NTD patients from the Dutch population. Sequence variation was studied by SSC analysis of the paired domain regions of the PAX1, PAX7, and PAX9 genes and of the complete PAX3 gene. In one patient with spina bifida, a mutation in the PAX1 gene was detected changing the conserved amino acid Gln to His at position 42 in the paired domain of the protein. The mutation was inherited through the maternal line from the unaffected grandmother and was not detected in 300 controls. In the PAX3 gene, variation was detected at several sites including a Thr/Lys amino acid substitution in exon 6. All alleles were present among patients and controls in about the same frequencies. However, an increased frequency of the rare allele of a silent polymorphism in exon 2 was found in NTD patients, but no significant association was observed (p = 0.06). No sequence variation was observed in the paired domain of the PAX7 and PAX9 genes. Our findings so far do not support a major role of the PAX genes examined in the aetiology of NTD. However, the detection of a mutation in PAX1 suggests that, in principle, this gene can act as a risk factor for human NTD. [less ▲]

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See detailAnalysis of limb patterning in BMP-7-deficient mice.
Hofmann, C.; Luo, G.; Balling, Rudi UL et al

in Developmental Genetics (1996), 19(1), 43-50

Bone morphogenetic proteins (BMPs) are polypeptide signaling molecules, belonging to the TGF-beta superfamily. They were originally identified by their ability to induce ectopic bone formation, but their ... [more ▼]

Bone morphogenetic proteins (BMPs) are polypeptide signaling molecules, belonging to the TGF-beta superfamily. They were originally identified by their ability to induce ectopic bone formation, but their expression patterns in embryos suggest multiple functions. BMP-7-deficient mice show among other mesodermal and skeletal patterning defects, polydactyly in the hindlimbs [Luo G, Hofmann C, Bronckers ALJJ, Sohocki M, Bradley A, Karsenty G (1995): Genes Dev 9:2808-2820; Dudley AT, Lyons KM, Robertson EJ (1995): Genes Dev 9:2795-2807]. Here we report a more detailed analysis of the limb phenotype in BMP-7-deficient mice using in situ hybridization to monitor expression of molecules implicated in patterning processes of the developing vertebrate limb. In previous studies we showed that Sonic hedgehog (Shh) was expressed normally, but Hoxd-13 expression in limb mesenchyme was lower in BMP-7 mutant limbs. Here we show that Hoxd-11 expression domains are also contracted and decreased in intensity in mutant limbs, suggesting that 5' genes of the Hoxd cluster are coordinately downregulated, while another Bmp, Bmp-2, which can be activated by Shh, is similarly expressed. The mutant limb buds are broader than normal buds, and fibroblast growth factor Fgf-8 is expressed throughout the extended ridge. However, expression of the homeobox gene Msx-1, which has been shown to be involved in epithelial-mesenchymal interactions during limb development, was decreased in the mesenchyme of BMP-7 mutant limbs. Taken together, our data suggest that BMP-7 is involved in regulating proliferation and/or epithelial-mesenchymal interactions in the developing limb. [less ▲]

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See detailExpression of avian Pax1 and Pax9 is intrinsically regulated in the pharyngeal endoderm, but depends on environmental influences in the paraxial mesoderm.
Muller, Tim UL; Ebensperger, C.; Neubuser, A. et al

in Developmental Biology (1996), 178(2), 403-17

Pax1 and Pax9 represent a subfamily of paired-box-containing genes. In vertebrates, Pax1 and Pax9 transcripts have been found specifically in mesodermal tissues and the pharyngeal endoderm. Pax1 ... [more ▼]

Pax1 and Pax9 represent a subfamily of paired-box-containing genes. In vertebrates, Pax1 and Pax9 transcripts have been found specifically in mesodermal tissues and the pharyngeal endoderm. Pax1 expression in the sclerotomes has been shown to be indispensable for proper formation of the axial skeleton, but expression of Pax1 in the endoderm has not been studied in detail. We have cloned the chick homologue of the murine Pax9 gene. Our results show that transcripts of Pax1 and Pax9 are first detectable in the prospective foregut endoderm of headfold-stage avian embryos. Endodermal expression correlates with the highly proliferative zones of the folding foregut and evaginating pharyngeal pouches. In later stages, Pax1 and Pax9 are expressed in overlapping but distinct patterns within the developing sclerotomes and limb buds. From grafting experiments we conclude that activation of pharyngeal Pax1 and Pax9 expression is an intrinsic property of the endoderm, not requiring midline structures or head mesoderm. In contrast, notochord is required to induce Pax1 in competent sclerotomes. Here we show that in vitro there is a cranio-caudal gradient of inductive capacity in the notochord. This coincides with the graded expression of Pax1 and Pax9 along the cranio-caudal axis in 2- to 3-day-old embryos. Furthermore, paraxial head mesoderm shows no competence to express Pax1. Finally, in vitro we find counteracting influences on notochord signaling by lateral tissues (lateral plate, intermediate mesoderm), leading to an inhibition of Sonic hedgehog (Shh) expression in notochord and floor plate, as well as Pax1 and Pax9 expression in sclerotomes. Taken together, our results demonstrate that different mechanisms regulate expression of Pax1 and Pax9 in foregut and sclerotome, but suggest a common function for both genes in the two tissues that is promoting proliferation and preventing fusion of neighboring blastemas. [less ▲]

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See detailPax genes and skeletal development.
Balling, Rudi UL; Helwig, U.; Nadeau, J. et al

in Annals of the New York Academy of Sciences (1996), 785

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See detailPax genes and sclerotome induction
Balling, Rudi UL; Neubüser, A; Christ, B

in Seminars in Cell and Developmental Biology (1996), (7), 129-136

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See detailA role for mel-18, a Polycomb group-related vertebrate gene, during theanteroposterior specification of the axial skeleton.
Akasaka, T.; Kanno, M.; Balling, Rudi UL et al

in Development (1996), 122(5), 1513-22

Segment identity in both invertebrates and vertebrates is conferred by spatially restricted distribution of homeotic gene products. In Drosophila, the expression of Homeobox genes during embryogenesis is ... [more ▼]

Segment identity in both invertebrates and vertebrates is conferred by spatially restricted distribution of homeotic gene products. In Drosophila, the expression of Homeobox genes during embryogenesis is initially induced by segmentation gene products and then maintained by Polycomb group and Trithorax group gene products. Polycomb group gene homologs are conserved in vertebrates. Murine mel-18 and closely related bmi-1 are homologous to posterior sex combs and suppressor two of zeste. Mel-18 protein mediates a transcriptional repression via direct binding to specific DNA sequences. To gain further insight into the function of Mel-18, we have inactivated the mel-18 locus by homologous recombination. Mice lacking mel-18 survive to birth and die around 4 weeks after birth after exhibiting strong growth retardation. Similar to the Drosophila posterior sex combs mutant, posterior transformations of the axial skeleton were reproducibly observed in mel-18 mutants. The homeotic transformations were correlated with ectopic expression of Homeobox cluster genes along the anteroposterior axis in the developing paraxial mesoderm. Surprisingly, mel-18-deficient phenotypes are reminiscent of bmi-1 mutants. These results indicate that the vertebrate Polycomb group genes mel-18 and bmi-1, like Drosophila Polycomb group gene products, might play a crucial role in maintaining the silent state of Homeobox gene expression during paraxial mesoderm development. [less ▲]

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See detailDrug Toxicity in Embryonic Development; Chapter 4: Axial Skeleton
Balling, Rudi UL

in Kavlock, R; Daston, G (Eds.) Handbook of Experimental Pharmacology (1996)

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See detailPax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation.
Wallin, J.; Eibel, H.; Neubuser, A. et al

in Development (1996), 122(1), 23-30

Pax1 is a transcriptional regulatory protein expressed during mouse embryogenesis and has been shown to have an important function in vertebral column development. Expression of Pax1 mRNA in the embryonic ... [more ▼]

Pax1 is a transcriptional regulatory protein expressed during mouse embryogenesis and has been shown to have an important function in vertebral column development. Expression of Pax1 mRNA in the embryonic thymus has been reported previously. Here we show that Pax1 protein expression in thymic epithelial cells can be detected throughout thymic development and in the adult. Expression starts in the early endodermal epithelium lining the foregut region and includes the epithelium of the third pharyngeal pouch, a structure giving rise to part of the thymus epithelium. In early stages of thymus development a large proportion of thymus cells expresses Pax1. With increasing age, the proportion of Pax1-expressing cells is reduced and in the adult mouse only a small fraction of cortical thymic stromal cells retains strong Pax1 expression. Expression of Pax1 in thymus epithelium is necessary for establishing the thymus microenvironment required for normal T cell maturation. Mutations in the Pax-1 gene in undulated mice affect not only the total size of the thymus but also the maturation of thymocytes. The number of thymocytes is reduced about 2- to 5-fold, affecting mainly the CD4+8+ immature and CD4+ mature thymocyte subsets. The expression levels of major thymocyte surface markers remains unchanged with the exception of Thy-1 which was found to be expressed at 3- to 4-fold higher levels. [less ▲]

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