C C Hui

Kumamoto University, Kumamoto, Kumamoto, Japan

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Publications (34)288.27 Total impact

  • Article: A Reply.
    JH Kim · PCW Kim · CC Hui ·

    Clinical Genetics 12/2001; 60(5):398. DOI:10.1016/j.ajog.2009.06.053 · 3.93 Impact Factor
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    R Haraguchi · R Mo · C.-C. Hui · J Motoyama · S Makino · T Shiroishi · W Gaffield · G Yamada ·
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    ABSTRACT: Coordinated growth and differentiation of external genitalia generates a proximodistally elongated structure suitable for copulation and efficient fertilization. The differentiation of external genitalia incorporates a unique process, i.e. the formation of the urethral plate and the urethral tube. Despite significant progress in molecular embryology, few attempts have been made to elucidate the molecular developmental processes for external genitalia. The sonic hedgehog (Shh) gene and its signaling genes have been found to be dynamically expressed during murine external genitalia development. Functional analysis by organ culture revealed that Shh could regulate mesenchymally expressed genes, patched 1 (Ptch1), bone morphogenetic protein 4 (Bmp4), Hoxd13 and fibroblast growth factor 10 (Fgf10), in the anlage: the genital tubercle (GT). Activities of Shh for both GT outgrowth and differentiation were also demonstrated. Shh(-/-) mice displayed complete GT agenesis, which is compatible with such observations. Furthermore, the regulation of apoptosis during GT formation was revealed for the first time. Increased cell death and reduced cell proliferation of the Shh(-/-) mice GT were shown. A search for alterations of Shh downstream gene expression identified a dramatic shift of Bmp4 gene expression from the mesenchyme to the epithelium of the Shh mutant before GT outgrowth. Regulation of mesenchymal Fgf10 gene expression by the epithelial Shh was indicated during late GT development. These results suggest a dual mode of Shh function, first by the regulation of initiating GT outgrowth, and second, by subsequent GT differentiation.
    Development 12/2001; 128(21):4241-50. · 6.46 Impact Factor
  • XW Meng · R Poon · XY Zhang · A Cheah · Q Ding · C C Hui · B Alman ·
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    ABSTRACT: Suppressor of fused (Su(fu)) is a negative regulator of the Hedgehog signaling pathway that controls the nuclear-cytoplasmic distribution of Gli/Ci transcription factors through direct protein-protein interactions. We show here that Su(fu) is present in a complex with the oncogenic transcriptional activator beta-catenin and functions as a negative regulator of T-cell factor (Tcf)-dependent transcription. Overexpression of Su(fu) in SW480 (APC(mut)) colon cancer cells in which beta-catenin protein is stabilized leads to a reduction in nuclear beta-catenin levels and in Tcf-dependent transcription. This effect of Su(fu) overexpression can be blocked by treatment of these cells with leptomycin B, a specific inhibitor of CRM1-mediated nuclear export. Overexpression of Su(fu) suppresses growth of SW480 (APC(mut)) tumor cells in nude mice. These observations indicate that Su(fu) negatively regulates beta-catenin signaling and that CRM-1-mediated nuclear export plays a role in this regulation. Our results also suggest that Su(fu) acts as a tumor suppressor.
    Journal of Biological Chemistry 11/2001; 276(43):40113-9. DOI:10.1074/jbc.M105317200 · 4.57 Impact Factor
  • C W Cheng · CC Hui · U Strähle · S H Cheng ·
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    ABSTRACT: Iroquois homeoproteins are prepatterning factors that positively regulate proneural genes and control neurogenesis. We have identified a zebrafish Iroquois gene, irx1, which is highly homologous to Xenopus Xiro1, Gallus c-Irx1 and mouse Irx1. Expression of irx1 was initially detected at the bud stage. By 16 h post-fertilization (hpf), irx1 expression was exclusively limited to the prospective midbrain and hindbrain. By 24 hpf, irx1 expression was clearly detected in the acousticovestibual ganglia, tectum, tegmentum, cerebellum and rhombomere 1 but not in rhombomere 2 or mid-hindbrain boundary.
    Development Genes and Evolution 10/2001; 211(8-9):442-4. DOI:10.1007/s004270100168 · 2.44 Impact Factor
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    ABSTRACT: Anorectal malformations are a common clinical problem affecting the development of the distal hindgut in infants. The spectrum of anorectal malformations ranges from the mildly stenotic anus to imperforate anus with a fistula between the urinary and intestinal tracts to the most severe form, persistent cloaca. The etiology, embryology, and pathogenesis of anorectal malformations are poorly understood and controversial. Sonic hedgehog (Shh) is an endoderm-derived signaling molecule that induces mesodermal gene expression in the chick hindgut. However, the role of Shh signaling in mammalian hindgut development is unknown. Here, we show that mutant mice with various defects in the Shh signaling pathway exhibit a spectrum of distal hindgut defects mimicking human anorectal malformations. Shh null-mutant mice display persistent cloaca. Mutant mice lacking Gli2 or Gli3, two zinc finger transcription factors involved in Shh signaling, respectively, exhibit imperforate anus with recto-urethral fistula and anal stenosis. Furthermore, persistent cloaca is also observed in Gli2(-/-);Gli3(+/-), Gli2(+/-);Gli3(-/-), and Gli2(-/-);Gli3(-/-) mice demonstrating a gene dose-dependent effect. Therefore, Shh signaling is essential for normal development of the distal hindgut in mice and mutations affecting Shh signaling produce a spectrum of anorectal malformations that may reveal new insights into their human disease equivalents.
    American Journal Of Pathology 09/2001; 159(2):765-74. DOI:10.1016/S0002-9440(10)61747-6 · 4.59 Impact Factor
  • Jh Kim · Pcw Kim · C C Hui ·
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    ABSTRACT: VACTERL represents a non-random association of congenital anomalies in humans of poorly known etiology and pathogenesis. From our mutant analysis of Gli genes, which encode transcription factors mediating Sonic hedgehog (Shh) signal transduction, we observed that defective Shh signaling leads to a spectrum of developmental anomalies in mice strikingly similar to those of VACTERL. In this review, we will discuss the function of the three Gli transcription factors in Shh signaling and mammalian development. We propose that VACTERL could be caused by defective Shh signaling during human embryogenesis and suggest that the Gli mutant mice can serve as useful models for studying the pathogenesis of VACTERL.
    Clinical Genetics 06/2001; 59(5):306-15. DOI:10.1034/j.1399-0004.2001.590503.x · 3.93 Impact Factor
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    Z Liu · JB Peng · R Mo · C.-c. Hui · C H Huang ·
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    ABSTRACT: Ammonium transporters play a key functional role in nitrogen uptake and assimilation in microorganisms and plants; however, little is known about their structural counterpart in mammals. Here, we report the molecular cloning and biochemical characterization of Rh type B glycoproteins, human RhBG and mouse Rhbg, two new members of the Rh family with distinct tissue specificities. The RhBG orthologues possess a conserved 12-transmembrane topology and most resemble bacterial and archaeal ammonium transporters. Human RHBG resides at chromosome 1q21.3, which harbors candidate genes for medullary cystic kidney disease, whereas mouse Rhbg is syntenic on chromosome 3. Northern blot and in situ hybridization revealed that RHBG and Rhbg are predominantly expressed in liver, kidney, and skin, the specialized organs involving ammonia genesis, excretion, or secretion. Confocal microscopy showed that RhBG is located in the plasma membrane and in some intracellular granules. Western blots of membrane proteins from stable HEK293 cells and from mouse kidney and liver confirmed this distribution. N-Glycanase digestion showed that RhBG/Rhbg has a carbohydrate moiety probably attached at the NHS motif on exoloop 1. Phylogenetic clustering, tissue-specific expression, and plasma membrane location suggest that RhBG homologous proteins are the long sought major ammonium transporters in mammalians.
    Journal of Biological Chemistry 02/2001; 276(2):1424-33. DOI:10.1074/jbc.M007528200 · 4.57 Impact Factor
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    Z Liu · Y Chen · R Mo · C.-c. Hui · J F Cheng · N Mohandas · C H Huang ·
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    ABSTRACT: In mammals, the Rh family includes the variable Rh polypeptides and invariant RhAG glycoprotein. These polytopic proteins are confined to the erythroid lineage and are assembled into a multisubunit complex essential for Rh antigen expression and plasma membrane integrity. Here, we report the characterization of RhCG and Rhcg, a pair of novel Rh homologues present in human and mouse nonerythroid tissues. Despite sharing a notable similarity to the erythroid forms, including the 12-transmembrane topological fold, theRHCG/Rhcg pair is distinct in chromosome location, genomic organization, promoter structure, and tissue-specific expression.RHCG and Rhcg map at 15q25 of human chromosome 15 and the long arm of mouse chromosome 7, respectively, each having 11 exons and a CpG-rich promoter. Northern blots detected kidney and testis as the major organs of RHCG or Rhcgexpression. In situ hybridization revealed strong expression of Rhcg in the kidney collecting tubules and testis seminiferous tubules. Confocal imaging of transiently expressed green fluorescence protein fusion proteins localized RhCG exclusively to the plasma membrane, a distribution confirmed by cellular fractionation and Western blot analysis. In vitrotranslation and ex vivo expression showed that RhCG carries a complex N-glycan, probably at the48NLS50 sequon of exoloop 1. These results pinpoint RhCG and Rhcg as novel polytopic membrane glycoproteins that may function as epithelial transporters maintaining normal homeostatic conditions in kidney and testis.
    Journal of Biological Chemistry 09/2000; 275(33):25641-51. DOI:10.1074/jbc.M003353200 · 4.57 Impact Factor
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    ABSTRACT: N-Linked glycosylation is a post-translational modification occurring in many eukaryotic secreted and surface-bound proteins and has impact on diverse physiological and pathological processes. Similarly important is the generation of glycosylphosphatidylinositol linkers, which anchor membrane proteins to the cell. Both protein modifications depend on the central nucleotide sugar UDP-N-acetylglucosamine (UDP-GlcNAc). The enzymatic reactions leading to generation of nucleotide sugars are established, yet most of the respective genes still await cloning. We describe the characterization of such a gene, EMeg32, which we identified based on its differential expression in murine hematopoietic precursor cells. We further demonstrate regulated expression during embryogenesis. EMeg32 codes for a 184-amino acid protein exhibiting glucosamine-6-phosphate acetyltransferase activity. It thereby holds a key position in the pathway toward de novo UDP-GlcNAc synthesis. Surprisingly, the protein associates with the cytoplasmic side of various intracellular membranes, accumulates prior to mitosis, and copurifies with the cdc48 homolog p97/valosin-containing protein.
    Journal of Biological Chemistry 05/2000; 275(17):12821-32. · 4.57 Impact Factor
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    ABSTRACT: The secreted factor Sonic hedgehog (SHH) is both required for and sufficient to induce multiple developmental processes, including ventralization of the CNS, branching morphogenesis of the lungs and anteroposterior patterning of the limbs. Based on analogy to the Drosophila Hh pathway, the multiple GLI transcription factors in vertebrates are likely to both transduce SHH signaling and repress Shh transcription. In order to discriminate between overlapping versus unique requirements for the three Gli genes in mice, we have produced a Gli1 mutant and analyzed the phenotypes of Gli1/Gli2 and Gli1/3 double mutants. Gli3(xt) mutants have polydactyly and dorsal CNS defects associated with ectopic Shh expression, indicating GLI3 plays a role in repressing Shh. In contrast, Gli2 mutants have five digits, but lack a floorplate, indicating that it is required to transduce SHH signaling in some tissues. Remarkably, mice homozygous for a Gli1(zfd )mutation that deletes the exons encoding the DNA-binding domain are viable and appear normal. Transgenic mice expressing a GLI1 protein lacking the zinc fingers can not induce SHH targets in the dorsal brain, indicating that the Gli1(zfd )allele contains a hypomorphic or null mutation. Interestingly, Gli1(zfd/zfd);Gli2(zfd/+), but not Gli1(zfd/zfd);Gli3(zfd/+) double mutants have a severe phenotype; most Gli1(zfd/zfd);Gli2(zfd/+) mice die soon after birth and all have multiple defects including a variable loss of ventral spinal cord cells and smaller lungs that are similar to, but less extreme than, Gli2(zfd/zfd) mutants. Gli1/Gli2 double homozygous mutants have more extreme CNS and lung defects than Gli1(zfd/zfd);Gli2(zfd/+) mutants, however, in contrast to Shh mutants, ventrolateral neurons develop in the CNS and the limbs have 5 digits with an extra postaxial nubbin. These studies demonstrate that the zinc-finger DNA-binding domain of GLI1 protein is not required for SHH signaling in mouse. Furthermore, Gli1 and Gli2, but not Gli1 and Gli3, have extensive overlapping functions that are likely downstream of SHH signaling.
    Development 05/2000; 127(8):1593-605. · 6.46 Impact Factor
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    ABSTRACT: Members of the Drosophila Iroquois homeobox gene family are implicated in the development of peripheral nervous system and the regionalization of wing and eye imaginal discs. Recent studies suggest that Xenopus Iroquois homeobox (Irx) genes are also involved in neurogenesis. Three mouse Irx genes, Irx1, Irx2 and Irx3, have been previously identified and are expressed with distinct spatio-temporal patterns during neurogenesis. We report here the cloning and expression analysis of two novel mouse Irx genes, Irx5 and Irx6. Although Irx5 and Irx6 proteins are structurally more related to one another, we find that Irx5 displays a developmental expression pattern strikingly similar to that of Irx3, whereas Irx6 expression resembles that of Irx1. Consistent with the notion that Mash1 is a putative target gene of the Irx proteins, all four Irx genes display an overlapping expression pattern with Mash1 in the developing CNS. In contrast, the Irx genes and Mash1 are expressed in complementary domains in the developing eye and olfactory epithelium.
    Mechanisms of Development 04/2000; 91(1-2):317-21. DOI:10.1016/S0925-4773(99)00263-4 · 2.44 Impact Factor

  • Nature Genetics 04/2000; 24(3):216-7. DOI:10.1038/73417 · 29.35 Impact Factor
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    ABSTRACT: The genetic, embryological, and pathogenetic aspects of hindgut development remain poorly understood. Recently, the morphogenetic pathway involving the Sonic hedgehog (Shh) gene has been shown essential to the normal development of many midaxial organs, including the foregut. This study reports genetically based murine models of congenital anorectal malformations (CAM) involving the Shh-responsive transcription factors, Gli2 and Gli3. Its purpose is to show the necessity of these 2 factors to normal hindgut development. Gli2-/- mutants were generated by a targeted deletion. Gli3-/- mutants are spontaneous mutants involving the Gli3 gene. Gli2-/- Gli3+/- mutants were generated by intercrossing double heterozygotes. Whole-mount midsagittal sections of the embryos were analyzed on embryonic days (E) 11.5 and E13.5. Gli3-/- mutants had anal stenosis and ectopic anus, and Gli2-/- mutants showed imperforate anus and rectourethral fistula. Gli2-/- Gli3+/- mutants had a cloacal abnormality. The phenotypic abnormalities observed in these mutant mice are identical to the spectrum of human CAM. The severity of the phenotype appears to reflect the gene dose. Gli2 and Gli3 play an important role in the normal development of murine hindgut. The results of this study provide, for the first time, a molecular basis for CAM.
    Journal of Pediatric Surgery 03/2000; 35(2):227-30; discussion 230-1. DOI:10.1016/S0022-3468(00)90014-9 · 1.39 Impact Factor
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    ABSTRACT: The Hedgehog (Hh) signaling pathway has critical functions during embryogenesis of both invertebrate and vertebrate species [1]; defects in this pathway in humans can cause developmental disorders as well as neoplasia [2]. Although the Gli1, Gli2, and Gli3 zinc finger proteins are known to be effectors of Hh signaling in vertebrates, the mechanisms regulating activity of these transcription factors remain poorly understood [3] [4]. In Drosophila, activity of the Gli homolog Cubitus interruptus (Ci) is likely to be modulated by its interaction with a cytoplasmic complex containing several other proteins [5] [6], including Costal2, Fused (Fu), and Suppressor of fused (Su(fu)), the last of which has been shown to interact directly with Ci [7]. We have cloned mouse Suppressor of fused (mSu(fu)) and detected its 4.5 kb transcript throughout embryogenesis and in several adult tissues. In cultured cells, mSu(fu) overexpression inhibited transcriptional activation mediated by Sonic hedgehog (Shh), Gli1 and Gli2. Co-immunoprecipitation of epitope-tagged proteins indicated that mSu(fu) interacts with Gli1, Gli2, and Gli3, and that the inhibitory effects of mSu(fu) on Gli1's transcriptional activity were mediated through interactions with both amino- and carboxy-terminal regions of Gli1. Gli1 was localized primarily to the nucleus of both HeLa cells and the Shh-responsive cell line MNS-70; co-expression with mSu(fu) resulted in a striking increase in cytoplasmic Gli1 immunostaining. Our findings indicate that mSu(fu) can function as a negative regulator of Shh signaling and suggest that this effect is mediated by interaction with Gli transcription factors.
    Current Biology 11/1999; 9(19):1119-22. DOI:10.1016/S0960-9822(99)80482-5 · 9.57 Impact Factor
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    H Sasaki · Y Nishizaki · CC Hui · M Nakafuku · H Kondoh ·
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    ABSTRACT: Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling in vertebrates. The question remains unanswered, however, as to how these Gli proteins participate in the Shh signaling pathway. In this study, regulatory activities associated with the Gli2 protein were investigated in relation to the Shh signaling. Although Gli2 acts as a weak transcriptional activator, it is in fact a composite of positive and negative regulatory domains. In cultured cells, truncation of the activation domain in the C-terminal half results in a protein with repressor activity, while removal of the repression domain at the N terminus converts Gli2 into a strong activator. In transgenic mouse embryos, N-terminally truncated Gli2, unlike the full length protein, activates a Shh target gene, HNF3beta, in the dorsal neural tube, thus mimicking the effect of Shh signal. This suggests that unmasking of the strong activation potential of Gli2 through modulation of the N-terminal repression domain is one of the key mechanisms of the Shh signaling. A similar regulatory mechanism involving the N-terminal region was also found for Gli3, but not for Gli1. When the Shh signal derived from the notochord is received by the neural plate, the widely expressed Gli2 and Gli3 proteins are presumably converted to their active forms in the ventral cells, leading to activation of transcription of their target genes, including Gli1.
    Development 10/1999; 126(17):3915-24. · 6.46 Impact Factor
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    A Partanen · J Motoyama · C C Hui ·
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    ABSTRACT: CBP (CREBBP/CREB-binding protein) and p300 are related signal-dependent transcriptional cofactors and histone acetyltransferases. They are both implicated in tumorigenesis and mutations in the human CBP gene have been found in Rubinstein-Taybi syndrome (RTS), which is characterized by multiple developmental defects and mental retardation. Studies with CBP and p300 mouse mutants indicate that both proteins are required for normal development, and that there is an essential gene dosage-sensitive role for these transcriptional cofactors in embryogenesis, cell differentiation and proliferation. Although it is generally believed that the expression of CBP and p300 is ubiquitous, we report here that they are developmentally regulated during mouse embryogenesis. In the developing CNS, CBP and p300 proteins were found throughout the newly formed neural plate, but their expression was later restricted to the dorsal parts of the developing neural tube. Later in neural development, CBP and p300 proteins could also be found in subsets of ventral neurons, including motor neurons and oligodendrocytes. During organogenesis, CBP and p300 proteins were expressed in specific cell types of the developing heart, vasculature, skin, lung and liver. Many of these tissues and organs are known to be affected in mutant mice lacking CBP and/or p300, and in RTS patients. Interestingly, while CBP and p300 proteins show extensive overlapping expression during mouse embryogenesis, we observed that their subcellular localization is developmentally regulated in several cell types. Taken together, our results suggest that there are common, as well as distinct, biochemical functions of CBP and p300 during mouse development.
    The International Journal of Developmental Biology 09/1999; 43(6):487-94. · 1.90 Impact Factor
  • Z Hardcastle · C C Hui · P T Sharpe ·
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    ABSTRACT: The Sonic Hedgehog (Shh) signalling pathway has been proposed to play an important role in mammalian tooth development. We describe the spatial and temporal expression of genes in this pathway during early tooth development and interpret these patterns in terms of the likely roles of Shh signalling. We show that the two putative receptors of the Shh ligand, Ptc and Ptch-2, localise in different cells, suggesting Shh may function in different ways as an epithelial and mesenchymal signal. Shh signalling has previously been shown, in other organs, to stimulate cell proliferation. In this paper we analyse the Fgf signalling pathway in Gli-2 mutants and propose a mechanism as to how Gli-2 may regulate cell proliferation in tooth development.
    Cellular and molecular biology 08/1999; 45(5):567-78. · 1.23 Impact Factor
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    ABSTRACT: The stress signaling kinase SEK1/MKK4 is a direct activator of stress-activated protein kinases (SAPKs; also called Jun-N-terminal kinases, JNKs) in response to a variety of cellular stresses, such as changes in osmolarity, metabolic poisons, DNA damage, heat shock or inflammatory cytokines. We have disrupted the sek1 gene in mice using homologous recombination. Sek1(-/- )embryos display severe anemia and die between embryonic day 10.5 (E10.5) and E12.5. Haematopoiesis from yolk sac precursors and vasculogenesis are normal in sek1(-/- )embryos. However, hepatogenesis and liver formation were severely impaired in the mutant embryos and E11.5 and E12.5 sek1(-/- )embryos had greatly reduced numbers of parenchymal hepatocytes. Whereas formation of the primordial liver from the visceral endoderm appeared normal, sek1(-/-) liver cells underwent massive apoptosis. These results provide the first genetic link between stress-responsive kinases and organogenesis in mammals and indicate that SEK1 provides a crucial and specific survival signal for hepatocytes.
    Development 03/1999; 126(3):505-16. · 6.46 Impact Factor
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    Jun Motoyama · Jason Liu · Rong Mo · Qi Ding · Martin Post · C C Hui ·
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    ABSTRACT: Foregut malformations (oesophageal atresia, tracheo-oesophageal fistula, lung anomalies and congenital stenosis of the oesophagus and trachea) are relatively common anomalies occurring in 1 in 2,000-5,000 live births, although their aetiology is poorly understood. The secreted glycoprotein Sonic hedgehog (Shh) has been suggested to act as an endodermal signal that controls hindgut patterning and lung growth. In mice, three zinc-finger transcription factors, Gli1, Gli2 and Gli3, have been implicated in the transduction of Shh signal. We report here that mutant mice lacking Gli2 function exhibit foregut defects, including stenosis of the oesophagus and trachea, as well as hypoplasia and lobulation defects of the lung. A reduction of 50% in the gene dosage of Gli3 in a Gli2-/- background resulted in oesophageal atresia with tracheo-oesophageal fistula and a severe lung phenotype. Mutant mice lacking both Gli2 and Gli3 function did not form oesophagus, trachea and lung. These results indicate that Gli2 and Gli3 possess specific and overlapping functions in Shh signalling during foregut development, and suggest that mutations in GLI genes may be involved in human foregut malformations.
    Nature Genetics 10/1998; 20(1):54-7. DOI:10.1038/1711 · 29.35 Impact Factor
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    Z Hardcastle · R Mo · C C Hui · P T Sharpe ·
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    ABSTRACT: The expression of genes involved in the Sonic Hedgehog signalling pathway, including Shh, Ptc, Smo, Gli1, Gli2 and Gli3, were found to be expressed in temporal and spatial patterns during early murine tooth development, suggestive of a role in early tooth germ initiation and subsequent epithelial-mesenchymal interactions. Of these Ptc, Smo, Gli1, Gli2 and Gli3 were expressed in epithelium and mesenchyme whereas Shh was only detected in epithelium. This suggests that Shh is involved in both lateral (epithelial-mesenchymal) and planar (epithelial-epithelial) signalling in early tooth development. Ectopic application of Shh protein to mandibular mesenchyme induced the expression of Ptc and Gli1. Addition of exogenous Shh protein directly into early tooth germs and adjacent to tooth germs, resulted in abnormal epithelial invagination, indicative of a role for Shh in epithelial cell proliferation. In order to assess the possible role of this pathway, tooth development in Gli2 and Gli3 mutant embryos was investigated. Gli2 mutants were found to have abnormal development of maxillary incisors, probably resulting from a mild holoprosencephaly, whereas Gli3 mutants had no major tooth abnormalities. Gli2/Gli3 double homozygous mutants did not develop any normal teeth and did not survive beyond embryonic day 14.5; however, Gli2(-/-); Gli3(+/-) did survive until birth and had small molars and mandibular incisors whereas maxillary incisor development was arrested as a rudimentary epithelial thickening. These results show an essential role for Shh signalling in tooth development that involves functional redundancy of downstream Gli genes.
    Development 09/1998; 125(15):2803-11. · 6.46 Impact Factor

Publication Stats

6k Citations
288.27 Total Impact Points


  • 2001
    • Kumamoto University
      • Center for Animal Resources and Development
      Kumamoto, Kumamoto, Japan
    • City University of Hong Kong
      • Department of Biology and Chemistry
      Chiu-lung, Kowloon City, Hong Kong
  • 1999-2001
    • SickKids
      Toronto, Ontario, Canada
  • 1996-2001
    • University of Toronto
      • • Hospital for Sick Children
      • • Department of Molecular Genetics
      Toronto, Ontario, Canada
  • 2000
    • New York Blood Center
      New York, New York, United States
  • 1994-1996
    • Samuel Lunenfeld Research Institute
      Toronto, Ontario, Canada