Scapula development is governed by genetic interactions ofPbx1with its family members and withEmx2via their cooperative control ofAlx1
Terence D. CapelliniG. VaccariElisabetta FerrettiSebastian FantiniMu HeMassimo PellegriniLaura QuintanaGiuseppina Di GiacomoJames SharpeLicia SelleriVincenzo Zappavigna
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Abstract:
The genetic pathways underlying shoulder blade development are largely unknown, as gene networks controlling limb morphogenesis have limited influence on scapula formation. Analysis of mouse mutants for Pbx and Emx2 genes has suggested their potential roles in girdle development. In this study, by generating compound mutant mice, we examined the genetic control of scapula development by Pbx genes and their functional relationship with Emx2. Analyses of Pbx and Pbx1;Emx2 compound mutants revealed that Pbx genes share overlapping functions in shoulder development and that Pbx1 genetically interacts with Emx2 in this process. Here, we provide a biochemical basis for Pbx1;Emx2 genetic interaction by showing that Pbx1 and Emx2 can bind specific DNA sequences as heterodimers. Moreover, the expression of genes crucial for scapula development is altered in these mutants, indicating that Pbx genes act upstream of essential pathways for scapula formation. In particular, expression of Alx1, an effector of scapula blade patterning, is absent in all compound mutants. We demonstrate that Pbx1 and Emx2 bind in vivo to a conserved sequence upstream of Alx1 and cooperatively activate its transcription via this potential regulatory element. Our results establish an essential role for Pbx1 in genetic interactions with its family members and with Emx2 and delineate novel regulatory networks in shoulder girdle development.Keywords:
EMX2
EMX2
Homeobox A1
HNF1B
Homeobox protein Nkx-2.5
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Homeobox A1
EMX2
Homeobox protein Nkx-2.5
HNF1B
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KNOX homeodomain proteins are encoded by knotted1-like homeobox (knox) genes that constitute a gene family in plants. Similar to the animal homeodomain proteins, KNOX proteins are considered to be key transcriptional regulators that control the expression of genes involved in plant organogenesis at the shoot apical meristem. Therefore, in order to understand the developmental processes in plants, it is important to elucidate the molecular mechanisms underlying KNOX protein regulation of gene expression. In this review, we discuss the structural features of KNOX proteins and the mechanisms by which they interact with and regulate target gene expression.
EMX2
Homeobox A1
Homeobox protein Nkx-2.5
Organogenesis
HNF1B
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The empty spiracles homeobox 2(EMX2) is homolog of the Drosophila head gap gene empty spiracles(ems) homeobox gene.The normal developments of human urogenital system and pelvis are dependent on the regulation of EMX2.EMX2 expressed in adult reproductive tract with cyclical changes,which regulated normal endometrial remodeling and blastocyst implantation.The upstream genes of EMX2 are HOXA10,Spastin and Ghrelin,while the downstream genes of EMX2 were reported less.EMX2 is related to the occurrence of endometriosis.With continuous study in future,we believe that the effect of EMX2 gene,as well as its clinical application in infertility and ART,will be revealed.
EMX2
Homeobox A1
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Homeobox genes have been demonstrated to play important roles during cancer differentiation and embryonic development. The subset of Iroquois-related homeobox genes (IRXs) have furthermore been demonstrated to be involved in several embryonic developmental processes such as patterning of the anterior-posterior and dorso-ventral axis, as well as specific regions of the central nervous system, and differentiation of the otic vesicle, branchial epithelium, and limbs. We have characterized a novel homeodomain protein and corresponding gene by means of computational biology. Since the protein sequence displayed high similarity to the human IRX proteins, the newly identified homeodomain protein was named Iroquois family related homeodomain protein (IFRX). The IFRX protein sequence was found to be highly conserved in vertebrates. The corresponding IFRX gene was located on chromosome 10p12.1 and is organized in seven exons. The protein is predicted to be localized to the nucleus, supporting evidence for a functional role as a transcription factor, as suggested by the existence of a homeodomain. Preliminary expression profiling by biocomputational means predicted a rather broad expression profile with expression in the bone marrow, brain, heart, kidney, liver, lung, pancreas, prostate, skeletal muscle, spinal cord, spleen and thymus. However, expression in several tissues seemed to be low. In addition, approximately one third of all available EST sequences were obtained from embryonic tissues, suggesting that IFRX has a role in embryonic development.
EMX2
Homeobox A1
Homeobox protein Nkx-2.5
PAX4
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Homeodomain proteins are well-characterized developmental regulators that control expression of target genes through sequence-specific DNA binding. The homeodomain forms a trihelical structure, with the third helix conferring specific interactions with the DNA major groove. A specific class of plant homeodomain proteins, called KNOX [KNOTTED1 (KN1)-like homeobox], also has the ability to signal between cells by directly trafficking through intercellular channels called plasmodesmata. Trafficking is mediated by a signal that is also contained within the homeodomain. Movement protein binding protein 2C was identified as a protein that interacts with the KN1 homeodomain and regulates the cell-to-cell trafficking of KN1 by sequestering the protein on microtubules. Therefore, KN1 has multiple potential cellular addresses, each of which is conferred by its homeodomain.
EMX2
Homeobox A1
Plasmodesma
Homeobox protein Nkx-2.5
HNF1B
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On the basis of the analysis of cDNA of three new homeobox-containing genes from human, chicken, and newt, a new class of homeobox genes Anf is characterized homologous to the Xanf-1 gene from Xenopus laevis, earlier cloned by us. These genes may be largely involved in the specification of embryonic subdivisions in the forebrain region of the embryo. The homeodomains of the proteins encoded by these genes differ greatly in the primary structure from all previously described homeobox genes. The high variability of the homeodomain sequences of the proteins of this class imply their rapid evolution.
Homeobox A1
Homeobox protein Nkx-2.5
HNF1B
EMX2
DLX5
Cloning (programming)
Forebrain
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The homeobox gene family is divided into classes based on similarity of sequence across the homeodomain. Representative members of discrete classes are often conserved widely throughout evolution and this can extend to their genomic organisation and biological function. In this paper we report the first complete cDNA sequence of a member of the GBX class of homeobox genes, the murine gene Gbx‐2 . Sequence comparisons indicate that this homeodomain class is highly conserved within vertebrates. The homeodomain differs at only three positions out of 60 and these can be used to subdivide the GBX class homeodomains into 2 sub‐classes.
Homeobox protein Nkx-2.5
EMX2
HNF1B
Homeobox A1
Conserved sequence
Sequence (biology)
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Abstract Over the past 25 years, numerous homeobox genes have been identified and their functions have been elucidated. Many studies in various plant species have revealed that Knotted‐like homeobox ( KNOX ) genes, the first identified homeobox gene in plants, play a profound role in shoot apical meristem organisation, maintenance, and leaf initiation. In addition to the KNOX gene, numerous other homeobox genes have been discovered (e.g., BEL1‐like homeodomain , Homeodomain leucine zipper , and WUSCHEL‐related homeobox genes) and play important roles in plant development. Moreover, in recent years, it has become clear that the homeobox genes also contribute to morphological diversity in plants. Key Concepts Homeobox (HB) genes encode a subset of transcription factors that contain a homeodomain In plants, several groups of HB genes (e.g., KNOTTED‐like homeobox , BEL1‐like homeodomain , Homeodomain leucine zipper , and WUSCHEL‐related homeobox genes) have been shown to have a distinct role in the development. The HB genes are involved in a wide range of developmental processes (e.g., stem cell maintenance in the SAM and floral meristems, cambium, and root meristem, leaf development, vascular development, embryo patterning, etc.). Recent studies revealed that changes in HB genes led to leaf form diversification and that HB genes are involved in alteration in response to environmental changes in a single plant.
Homeobox A1
EMX2
Homeobox protein Nkx-2.5
HNF1B
DLX5
CDX2
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We have cloned and sequenced a cDNA encoding the mammalian homologue of Distal-less 3 (Dlx-3) from a rat embryonic brain cDNA library. The primary structure of rat Dlx-3 showed a cDNA with an open reading frame of 290 amino acids with a molecular weight of 31 kDa harboring a homeodomain sequence characteristic of the Distal-less homoeobox gene. In addition to the highly conserved homeodomain sequence, we newly found the consensus motifs in the N-terminal and C-terminal region, which were specifically conserved among Distal-less members of different species. Phylogenetic analysis of the Distal-less homeodomain sequence also showed a possible association between the sequence similarities in the homeodomain and the spatial specifications of homeobox genes expressed in the developing central nervous system.
EMX2
Homeobox A1
Homeobox protein Nkx-2.5
HNF1B
Cloning (programming)
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