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Robert Finkelstein - One of the best experts on this subject based on the ideXlab platform.
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Epidermal growth factor receptor signaling activates Orthodenticle expression during Drosophila head development.
DNA and cell biology, 2000Co-Authors: Amr Amin, Robert FinkelsteinAbstract:The relation between signal transduction pathways and the genes that specify regional identity remains poorly understood. We investigated the interaction between the epidermal growth factor receptor (EGFR) pathway and the homeobox gene Orthodenticle (otd), which specifies cell fate during head development. Previous studies of head formation in Drosophila melanogaster demonstrated that reducing either EGFR signaling or otd expression in the imaginal primordium of the dorsal head capsule eliminates the ocelli and other dorsal head structures. Here, we show that blocking EGFR signaling reduces otd expression and that activating EGFR signaling outside this primordium induces ectopic otd expression. We also demonstrate that loss of EGFR can be rescued by constitutive otd expression. Our results indicate that otd is a downstream target of the EGFR pathway during head development.
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Equivalence of the fly Orthodenticle gene and the human OTX genes in embryonic brain development of Drosophila
Development (Cambridge England), 1998Co-Authors: Sandra Leuzinger, Katsuo Furukubo-tokunaga, Frank Hirth, Antonio Simeone, Daniel W. Gerlich, Dario Acampora, Walter J. Gehring, Robert Finkelstein, Heinrich ReichertAbstract:Members of the Orthodenticle gene family are essential for embryonic brain development in animals as diverse as insects and mammals. In Drosophila, mutational inactivation of the Orthodenticle gene results in deletions in anterior parts of the embryonic brain and in defects in the ventral nerve cord. In the mouse, targeted elimination of the homologous Otx2 or Otx1 genes causes defects in forebrain and/or midbrain development. To determine the morphogenetic properties and the extent of evolutionary conservation of the Orthodenticle gene family in embryonic brain development, genetic rescue experiments were carried out in Drosophila. Ubiquitous overexpression of the Orthodenticle gene rescues both the brain defects and the ventral nerve cord defects in Orthodenticle mutant embryos; morphology and nervous system-specific gene expression are restored. Two different time windows exist for the rescue of the brain versus the ventral nerve cord. Ubiquitous overexpression of the human OTX1 or OTX2 genes also rescues the brain and ventral nerve cord phenotypes in Orthodenticle mutant embryos; in the brain, the efficiency of morphological rescue is lower than that obtained with overexpression of Orthodenticle. Overexpression of either Orthodenticle or the human OTX gene homologs in the wild-type embryo results in ectopic neural structures. The rescue of highly complex brain structures in Drosophila by either fly or human Orthodenticle gene homologs indicates that these genes are interchangeable between vertebrates and invertebrates and provides further evidence for an evolutionarily conserved role of the Orthodenticle gene family in brain development.
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Establishing primordia in the Drosophila eye-antennal imaginal disc: the roles of decapentaplegic, wingless and hedgehog
Development (Cambridge England), 1997Co-Authors: Julien Royet, Robert FinkelsteinAbstract:The eye-antennal imaginal discs of Drosophila melanogaster form the head capsule of the adult fly. Unlike the limb primordia, each eye-antennal disc gives rise to morphologically and functionally distinct structures. As a result, these discs provide an excellent model system for determining how the fates of primordia are specified during development. In this study, we investigated how the adjacent primordia of the compound eye and dorsal head vertex are specified. We show that the genes wingless (wg) and Orthodenticle (otd) are expressed throughout the entire second instar eye-antennal disc, conferring a default fate of dorsal vertex cuticle. Activation of decapentaplegic (dpp) expression in the posterior eye disc eliminates wg and otd expression, thereby permitting eye differentiation. We also demonstrate that otd is activated by wg in the vertex primordium. Finally, we show that early activation of dpp depends on hedgehog (hh) expression in the eye anlage prior to morphogenetic furrow formation.
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Two Orthodenticle-related genes in the short-germ beetle Tribolium castaneum
Development genes and evolution, 1996Co-Authors: Susan J. Brown, Bernhard Hausdorf, Diethard Tautz, Robin E. Denell, Robert FinkelsteinAbstract:To investigate the molecular basis of head evolution, we searched for genes related to the Drosophila Orthodenticle (otd) homeobox gene in the short-germ beetle Tribolium castaneum. Unexpectedly, we found that there are two otd-related genes in Tribolium, with predicted homeodomains highly similar to that of the single Drosophila gene. One of the two genes (Tc otd-1) is more related in both amino acid sequence and expression pattern to fruitfly otd. Tc otd-1 is expressed in a broad anterior stripe in the blastoderm embryo, suggesting a role in early head segmentation similar to that of the Drosophila gene. The second gene (Tc otd-2) is more similar in sequence to the otd-related genes isolated from different vertebrate species (the Otx gene family). Tc otd-2 is not transcribed in the blastoderm, but is expressed later in more limited subsets of cells in the anterior brain. Both Tribolium genes and the Drosophila gene are, unlike the vertebrate genes, also expressed at the developing ventral midline of the embryo. Our results are consistent with the idea that an otd/Otx gene specified anterior head structures in the last ancestor common to arthropods and vertebrates. Within the arthropod lineage, we propose that this gene acquired a function in cells at the developing midline prior to the duplication that generated the two Tribolium genes.
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hedgehog, wingless and Orthodenticle specify adult head development in Drosophila.
Development (Cambridge England), 1996Co-Authors: Julien Royet, Robert FinkelsteinAbstract:The adult head capsule of Drosophila forms primarily from the eye-antennal imaginal discs. Here, we demonstrate that the head primordium is patterned differently from the discs which give rise to the appendages. We show that the segment polarity genes hedgehog and wingless specify the identities of specific regions of the head capsule. During eye-antennal disc development, hedgehog and wingless expression initially overlap, but subsequently segregate. This regional segregation is critical to head specification and is regulated by the Orthodenticle homeobox gene. We also show that Orthodenticle is a candidate hedgehog target gene during early eye-antennal disc development.
Hidetoshi Saiga - One of the best experts on this subject based on the ideXlab platform.
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Vegetal cell fate specification and anterior neuroectoderm formation by Hroth, the ascidian homologue of Orthodenticle/otx
Mechanisms of Development, 1999Co-Authors: Shuichi Wada, Hidetoshi SaigaAbstract:To obtain insights into the mechanisms of gastrulation and neural tube formation, we studied the function and regulation of expression of Hroth, the ascidian homologue of Orthodenticle/otx, during embryogenesis. Microinjection of synthetic Hroth mRNA into fertilized eggs led to embryos with an expanded trunk and a reduced tail. In these embryos, development of notochord and muscle was effected. Also, Hroth overexpression caused ectopic formation of anterior neuroectoderm, along with suppression of epidermis development, even in the absence of cell-cell interaction. Furthermore, we demonstrated that ectodermal expression of Hroth requires an inductive influence from the vegetal hemisphere cells. These data suggest roles of Hroth in both specification of mesoendodermal cells and anterior neuroectoderm formation.
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vegetal cell fate specification and anterior neuroectoderm formation by hroth the ascidian homologue of Orthodenticle otx
Mechanisms of Development, 1999Co-Authors: Shuichi Wada, Hidetoshi SaigaAbstract:To obtain insights into the mechanisms of gastrulation and neural tube formation, we studied the function and regulation of expression of Hroth, the ascidian homologue of Orthodenticle/otx, during embryogenesis. Microinjection of synthetic Hroth mRNA into fertilized eggs led to embryos with an expanded trunk and a reduced tail. In these embryos, development of notochord and muscle was effected. Also, Hroth overexpression caused ectopic formation of anterior neuroectoderm, along with suppression of epidermis development, even in the absence of cell-cell interaction. Furthermore, we demonstrated that ectodermal expression of Hroth requires an inductive influence from the vegetal hemisphere cells. These data suggest roles of Hroth in both specification of mesoendodermal cells and anterior neuroectoderm formation.
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Homeobox Genes Exhibit Evolutionary Conserved Regionalization in the Central Nervous System of an Ascidian Larva
Zoological science, 1996Co-Authors: You Katsuyama, Shuichi Wada, Hidetoshi SaigaAbstract:Animals in each subgroup of the phylum Chordata exhibit a similar process by which they form a tubular central nervous system (CNS). However, little is known about spatial relationship among the CNSs of chordates; vertebrates, cephalochordates and urochordates (tunicates). Ascidians constitute a major animal group in the subphylum Urochordata. In the present study, we examined the expression patterns of labial and Orthodenticle related genes of the ascidian, Halocynthia roretzi, in the developing larval CNS. These homeobox genes exhibited region-specific expression patterns that are strikingly similar to those of murine Hoxb-1 and Otx2. The regionalization as characterized by the expression of these genes supports the division of the ascidian larval CNS suggested by the previous morphological studies. Furthermore, conservation of the expression pattern of the homeobox genes suggests that such regionalization occurred in the CNS of a putative common ancestor of chordates.
Reinhard Schröder - One of the best experts on this subject based on the ideXlab platform.
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From development to biodiversity--Tribolium castaneum, an insect model organism for short germband development.
Development genes and evolution, 2008Co-Authors: Reinhard Schröder, Anke Beermann, Nadine Wittkopp, Rebekka LutzAbstract:Insect embryogenesis is best understood in the fruit fly Drosophila. However, Drosophila embryogenesis shows evolutionary-derived features: anterior patterning is controlled by a highly derived Hox gene bicoid, the body segments form almost simultaneously and appendages develop from imaginal discs. In contrast, embryogenesis of the red flour beetle Tribolium castaneum displays typical features in anterior patterning, axis and limb formation shared with most insects, other arthropods as well as with vertebrates. Anterior patterning depends on the conserved homeobox gene Orthodenticle, the main body axis elongates sequentially and limbs grow continuously starting from an appendage bud. Thus, by analysing developmental processes in the beetle at the molecular and cellular level, inferences can be made for similar processes in other arthropods. With the completion of sequencing the Tribolium genome, the door is now open for post-genomic studies such as RNA expression profiling, proteomics and functional genomics to identify beetle-specific gene circuits.
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From development to biodiversity—Tribolium castaneum, an insect model organism for short germband development
Development Genes and Evolution, 2008Co-Authors: Reinhard Schröder, Anke Beermann, Nadine Wittkopp, Rebekka LutzAbstract:Insect embryogenesis is best understood in the fruit fly Drosophila . However, Drosophila embryogenesis shows evolutionary-derived features: anterior patterning is controlled by a highly derived Hox gene bicoid , the body segments form almost simultaneously and appendages develop from imaginal discs. In contrast, embryogenesis of the red flour beetle Tribolium castaneum displays typical features in anterior patterning, axis and limb formation shared with most insects, other arthropods as well as with vertebrates. Anterior patterning depends on the conserved homeobox gene Orthodenticle , the main body axis elongates sequentially and limbs grow continuously starting from an appendage bud. Thus, by analysing developmental processes in the beetle at the molecular and cellular level, inferences can be made for similar processes in other arthropods. With the completion of sequencing the Tribolium genome, the door is now open for post-genomic studies such as RNA expression profiling, proteomics and functional genomics to identify beetle-specific gene circuits.
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The genes Orthodenticle and hunchback substitute for bicoid in the beetle Tribolium.
Nature, 2003Co-Authors: Reinhard SchröderAbstract:In Drosophila, the morphogen Bicoid organizes anterior patterning in a concentration-dependent manner by activating the transcription of target genes such as Orthodenticle (otd) and hunchback (hb), and by repressing the translation of caudal. Homologues of the bicoid gene have not been isolated in any organism apart from the higher Dipterans. In fact, head and thorax formation in other insects is poorly understood. To elucidate this process in a short-germband insect, I analysed the function of the conserved genes Orthodenticle-1 (otd-1) and hb in the flour beetle Tribolium castaneum. Here I show that, in contrast to Drosophila, Tribolium otd-1 messenger RNA is maternally inherited by the embryo. Reduction of Tribolium otd-1 levels by RNA interference (RNAi) results in headless embryos. This shows that otd-1 is required for anterior patterning in Tribolium. As in Drosophila, Tribolium hb specifies posterior gnathal and thoracic segments. The head, thorax and the anterior abdomen fail to develop in otd-1/hb double-RNAi embryos. This phenotype is similar to that of strong bicoid mutants in Drosophila. I propose that otd-1 and hb are part of an ancestral anterior patterning system.
Katsuaki Motomura - One of the best experts on this subject based on the ideXlab platform.
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Heterozygous Orthodenticle Homeobox 2 Mutations Are Associated with Variable Pituitary Phenotype
Endocrine Reviews, 2010Co-Authors: Sumito Dateki, Kitaro Kosaka, Noriyuki Azuma, Susumu Yokoya, Toshihiro Tajima, Kosei Hasegawa, Koji Muroya, Masanori Adachi, Hiroyuki Tanaka, Katsuaki MotomuraAbstract:ABSTRACT Context Although recent studies have suggested a positive role of OTX2 in pituitary as well as ocular development and function, detailed pituitary phenotypes in OTX2 mutations and OTX2 target genes for pituitary function other than HESX1 and POU1F1 remain to be determined. Objective We aimed to examine such unresolved issues. Subjects We studied 94 Japanese patients with various ocular or pituitary abnormalities. Results We identified heterozygous p.K74fsX103 in case 1, p.A72fsX86 in case 2, p.G188X in two unrelated cases (3 and 4), and a 2,860,561-bp microdeletion involving OTX2 in case 5. Clinical studies revealed isolated GH deficiency in cases 1 and 5; combined pituitary hormone deficiency in case 3; abnormal pituitary structures in cases 1, 3, and 5; and apparently normal pituitary function in cases 2 and 4, together with ocular anomalies in cases 1-5. The wild-type Orthodenticle homeobox 2 (OTX2) protein transactivated the GNRH1 promoter as well as the HESX1, POU1F1, and IRBP (interstitial retinoid-binding protein) promoters, whereas the p.K74fsX103-OTX2 and p.A72fsX86-OTX2 proteins had no transactivation functions and the p.G188X-OTX2 protein had reduced (∼50%) transactivation functions for the four promoters, with no dominant-negative effect. cDNA screening identified positive OTX2 expression in the hypothalamus. Conclusions The results imply that OTX2 mutations are associated with variable pituitary phenotype, with no genotype-phenotype correlations, and that OTX2 can transactivate GNRH1 as well as HESX1 and POU1F1.
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Heterozygous Orthodenticle Homeobox 2 Mutations Are Associated with Variable Pituitary Phenotype
The Journal of clinical endocrinology and metabolism, 2009Co-Authors: Sumito Dateki, Kitaro Kosaka, Noriyuki Azuma, Susumu Yokoya, Toshihiro Tajima, Koji Muroya, Masanori Adachi, Hiroyuki Tanaka, Kousei Hasegawa, Katsuaki MotomuraAbstract:Context: Although recent studies have suggested a positive role of OTX2 in pituitary as well as ocular development and function, detailed pituitary phenotypes in OTX2 mutations and OTX2 target genes for pituitary function other than HESX1 and POU1F1 remain to be determined. Objective: We aimed to examine such unresolved issues. Subjects: We studied 94 Japanese patients with various ocular or pituitary abnormalities. Results: We identified heterozygous p.K74fsX103 in case 1, p.A72fsX86 in case 2, p.G188X in two unrelated cases (3 and 4), and a 2,860,561-bp microdeletion involving OTX2 in case 5. Clinical studies revealed isolated GH deficiency in cases 1 and 5; combined pituitary hormone deficiency in case 3; abnormal pituitary structures in cases 1, 3, and 5; and apparently normal pituitary function in cases 2 and 4, together with ocular anomalies in cases 1–5. The wild-type Orthodenticle homeobox 2 (OTX2) protein transactivated the GNRH1 promoter as well as the HESX1, POU1F1, and IRBP (interstitial retin...
Shuichi Wada - One of the best experts on this subject based on the ideXlab platform.
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Vegetal cell fate specification and anterior neuroectoderm formation by Hroth, the ascidian homologue of Orthodenticle/otx
Mechanisms of Development, 1999Co-Authors: Shuichi Wada, Hidetoshi SaigaAbstract:To obtain insights into the mechanisms of gastrulation and neural tube formation, we studied the function and regulation of expression of Hroth, the ascidian homologue of Orthodenticle/otx, during embryogenesis. Microinjection of synthetic Hroth mRNA into fertilized eggs led to embryos with an expanded trunk and a reduced tail. In these embryos, development of notochord and muscle was effected. Also, Hroth overexpression caused ectopic formation of anterior neuroectoderm, along with suppression of epidermis development, even in the absence of cell-cell interaction. Furthermore, we demonstrated that ectodermal expression of Hroth requires an inductive influence from the vegetal hemisphere cells. These data suggest roles of Hroth in both specification of mesoendodermal cells and anterior neuroectoderm formation.
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vegetal cell fate specification and anterior neuroectoderm formation by hroth the ascidian homologue of Orthodenticle otx
Mechanisms of Development, 1999Co-Authors: Shuichi Wada, Hidetoshi SaigaAbstract:To obtain insights into the mechanisms of gastrulation and neural tube formation, we studied the function and regulation of expression of Hroth, the ascidian homologue of Orthodenticle/otx, during embryogenesis. Microinjection of synthetic Hroth mRNA into fertilized eggs led to embryos with an expanded trunk and a reduced tail. In these embryos, development of notochord and muscle was effected. Also, Hroth overexpression caused ectopic formation of anterior neuroectoderm, along with suppression of epidermis development, even in the absence of cell-cell interaction. Furthermore, we demonstrated that ectodermal expression of Hroth requires an inductive influence from the vegetal hemisphere cells. These data suggest roles of Hroth in both specification of mesoendodermal cells and anterior neuroectoderm formation.
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Homeobox Genes Exhibit Evolutionary Conserved Regionalization in the Central Nervous System of an Ascidian Larva
Zoological science, 1996Co-Authors: You Katsuyama, Shuichi Wada, Hidetoshi SaigaAbstract:Animals in each subgroup of the phylum Chordata exhibit a similar process by which they form a tubular central nervous system (CNS). However, little is known about spatial relationship among the CNSs of chordates; vertebrates, cephalochordates and urochordates (tunicates). Ascidians constitute a major animal group in the subphylum Urochordata. In the present study, we examined the expression patterns of labial and Orthodenticle related genes of the ascidian, Halocynthia roretzi, in the developing larval CNS. These homeobox genes exhibited region-specific expression patterns that are strikingly similar to those of murine Hoxb-1 and Otx2. The regionalization as characterized by the expression of these genes supports the division of the ascidian larval CNS suggested by the previous morphological studies. Furthermore, conservation of the expression pattern of the homeobox genes suggests that such regionalization occurred in the CNS of a putative common ancestor of chordates.