Role of Hox genes in regulating digit patterning

The distal part of the tetrapod limb, the autopod, is characterized by the presence of digits. The digits display a wide diversity of shapes and number reflecting selection pressure for functional adaptation. Despite extensive study, the different aspects of digit patterning, as well as the factors and mechanisms involved are not completely understood. Here, we review the evidence implicating Hox proteins in digit patterning and the interaction between Hox genes and the Sonic hedgehog/Gli3 pathway, the other major regulator of digit number and identity. Currently, it is well accepted that a self-organizing Turing-type mechanism underlies digit patterning, this being understood as the establishment of an iterative arrangement of digit/interdigit in the hand plate. We also discuss the involvement of 5’ Hox genes in regulating digit spacing in the digital plate and therefore the number of digits formed in this self-organizing system.

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A Systematic Review on HOX Genes as Potential Biomarkers in Colorectal Cancer: An Emerging Role of HOXB9

International Journal of Molecular Sciences ◽

10.3390/ijms222413429 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13429

Author(s):

Eirini Martinou ◽

Giulia Falgari ◽

Izhar Bagwan ◽

Angeliki M. Angelidi

Keyword(s):

Poor Prognosis ◽

Tumour Growth ◽

Hox Genes ◽

Distant Metastases ◽

Metastatic Potential ◽

Hox Proteins ◽

Aberrant Expression ◽

Mesenchymal Transition ◽

The Impact

Emerging evidence shows that Homeobox (HOX) genes are important in carcinogenesis, and their dysregulation has been linked with metastatic potential and poor prognosis. This review (PROSPERO-CRD42020190953) aims to systematically investigate the role of HOX genes as biomarkers in CRC and the impact of their modulation on tumour growth and progression. The MEDLINE, EMBASE, Web of Science and Cochrane databases were searched for eligible studies exploring two research questions: (a) the clinicopathological and prognostic significance of HOX dysregulation in patients with CRC and (b) the functional role of HOX genes in CRC progression. Twenty-five studies enrolling 3003 CRC patients, showed that aberrant expression of HOX proteins was significantly related to tumour depth, nodal invasion, distant metastases, advanced stage and poor prognosis. A post-hoc meta-analysis on HOXB9 showed that its overexpression was significantly associated with the presence of distant metastases (pooled OR 4.14, 95% CI 1.64–10.43, I2 = 0%, p = 0.003). Twenty-two preclinical studies showed that HOX proteins are crucially related to tumour growth and metastatic potential by affecting cell proliferation and altering the expression of epithelial-mesenchymal transition modulators. In conclusion, HOX proteins may play vital roles in CRC progression and are associated with overall survival. HOXB9 may be a critical transcription factor in CRC.

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Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut

Development ◽

10.1242/dev.121.10.3163 ◽

1995 ◽

Vol 121 (10) ◽

pp. 3163-3174 ◽

Cited By ~ 80

Author(s):

D.J. Roberts ◽

R.L. Johnson ◽

A.C. Burke ◽

C.E. Nelson ◽

B.A. Morgan ◽

...

Keyword(s):

Sonic Hedgehog ◽

Target Genes ◽

Hox Genes ◽

Ectopic Expression ◽

Secreted Protein ◽

Gut Development ◽

Visceral Mesoderm ◽

Homologous Genes ◽

Inductive Signal

Reciprocal inductive signals between the endoderm and mesoderm are critical to vertebrate gut development. Sonic hedgehog encodes a secreted protein known to act as an inductive signal in several regions of the developing embryo. In this report, we provide evidence to support the role of Sonic hedgehog and its target genes Bmp-4 and the Abd-B-related Hox genes in the induction and patterning the chick hindgut. Sonic is expressed in the definitive endoderm at the earliest stage of chick gut formation. Immediately subjacent to Sonic expression in the caudal endoderm is undifferentiated mesoderm, later to become the visceral mesoderm of the hindgut. Genes expressed within this tissue include Bmp-4 (a TGF-beta relative implicated in proper growth of visceral mesoderm) and members of the Abd-B class of Hox genes (known regulators of pattern in many aspects of development). Using virally mediated misexpression, we show that Sonic hedgehog is sufficient to induce ectopic expression of Bmp-4 and specific Hoxd genes within the mesoderm. Sonic therefore appears to act as a signal in an epithelial-mesenchymal interaction in the earliest stages of chick hindgut formation. Gut pattern is evidenced later in gut morphogenesis with the presence of anatomic boundaries reflecting phenotypically and physiologically distinct regions. The expression pattern of the Abd-b-like Hox genes remains restricted in the hindgut and these Hox expression domains reflect gut morphologic boundaries. This finding strongly supports a role for these genes in determining the adult gut phenotype. Our results provide the basis for a model to describe molecular controls of early vertebrate hindgut development and patterning. Expression of homologous genes in Drosophila suggest that aspects of gut morphogenesis may be regulated by similar inductive networks in the two organisms.

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Hox genes in the coordination of embryonic development. Model of hourglass in the description of vertebrate ontogenesis

Journal of Education, Health and Sport ◽

10.12775/jehs.2021.11.12.002 ◽

2021 ◽

Vol 11 (12) ◽

pp. 24-37

Author(s):

Sergey Dolomatov ◽

Vera Kazakova ◽

Walery Zukow

Keyword(s):

Embryonic Development ◽

Tissue Regeneration ◽

Target Genes ◽

Hox Genes ◽

Development Model ◽

Tissue Morphogenesis ◽

Hox Proteins ◽

Temporal And Spatial

The paper analyzes the role of HOX genes in the processes of embryonic development of vertebrates. Based on the analysis, it is concluded that HOX genes are the most important regulators of embryonic development. The HOX genes predominantly realize their influence through specific HOX proteins that have the ability to regulate the expression of target genes. The order of expression of the HOX genes, as a rule, obeys the rule of temporal and spatial colinearity. This mechanism determines the temporal and spatial course of tissue morphogenesis during embryonic development and tissue regeneration in organisms that have reached the stage of maturity. The process of embryo morphogenesis, determined by highly conserved HOX genes, explains the appearance of the phylotypic period - the stage of embryonic development of vertebrates, at which embryos of different classes of vertebrates have distinct morphological similarities.

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The Self-Organizing Society: The Role of Institutions

SSRN Electronic Journal ◽

10.2139/ssrn.2840637 ◽

2016 ◽

Cited By ~ 1

Author(s):

John E. Stewart

Keyword(s):

The Self ◽

Self Organizing

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Dysregulation of HOX as a Potential Therapeutic Target in Breast Cancer

Current Medicinal Chemistry ◽

10.2174/0929867327666201102115327 ◽

2020 ◽

Vol 27 ◽

Author(s):

Ji-Yeon Lee ◽

Myoung Hee Kim

Keyword(s):

Breast Cancer ◽

Hox Genes ◽

Therapeutic Potential ◽

Expression Patterns ◽

Genome Structure ◽

Control Cell ◽

Three Dimensional ◽

Cellular Processes ◽

Hox Protein

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

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Hox dosage contributes to flight appendage morphology in Drosophila

Nature Communications ◽

10.1038/s41467-021-23293-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Rachel Paul ◽

Guillaume Giraud ◽

Katrin Domsch ◽

Marilyne Duffraisse ◽

Frédéric Marmigère ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Differential Expression ◽

Hox Genes ◽

Expression Profiles ◽

Fruit Fly ◽

Insect Species ◽

Wing Morphology ◽

Hox Proteins ◽

Spatial Expression ◽

Flying Insects

AbstractFlying insects have invaded all the aerial space on Earth and this astonishing radiation could not have been possible without a remarkable morphological diversification of their flight appendages. Here, we show that characteristic spatial expression profiles and levels of the Hox genes Antennapedia (Antp) and Ultrabithorax (Ubx) underlie the formation of two different flight organs in the fruit fly Drosophila melanogaster. We further demonstrate that flight appendage morphology is dependent on specific Hox doses. Interestingly, we find that wing morphology from evolutionary distant four-winged insect species is also associated with a differential expression of Antp and Ubx. We propose that variation in the spatial expression profile and dosage of Hox proteins is a major determinant of flight appendage diversification in Drosophila and possibly in other insect species during evolution.

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Differences in the levels of Sonic hedgehog protein during early foregut development caused by exposure to Adriamycin give clues to the role of the Shh gene in oesophageal atresia

Pediatric Surgery International ◽

10.1007/s00383-003-0959-8 ◽

2003 ◽

Vol 19 (6) ◽

pp. 463-466 ◽

Cited By ~ 20

Author(s):

Dejan Arsic ◽

Jacqui Keenan ◽

Qi Bao Quan ◽

Spencer Beasley

Keyword(s):

Sonic Hedgehog ◽

Oesophageal Atresia

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The Role of Sonic Hedgehog-Gli2 Pathway in the Masculinization of External Genitalia

Endocrinology ◽

10.1210/en.2011-0263 ◽

2011 ◽

Vol 152 (7) ◽

pp. 2894-2903 ◽

Cited By ~ 42

Author(s):

Shinichi Miyagawa ◽

Daisuke Matsumaru ◽

Aki Murashima ◽

Akiko Omori ◽

Yoshihiko Satoh ◽

...

Keyword(s):

Signaling Pathway ◽

Sonic Hedgehog ◽

Hedgehog Signaling ◽

External Genitalia ◽

Sexually Dimorphic ◽

Hedgehog Signaling Pathway ◽

Initial Development ◽

Urethral Plate ◽

Male External Genitalia

During embryogenesis, sexually dimorphic organogenesis is achieved by hormones produced in the gonad. The external genitalia develop from a single primordium, the genital tubercle, and their masculinization processes depend on the androgen signaling. In addition to such hormonal signaling, the involvement of nongonadal and locally produced masculinization factors has been unclear. To elucidate the mechanisms of the sexually dimorphic development of the external genitalia, series of conditional mutant mouse analyses were performed using several mutant alleles, particularly focusing on the role of hedgehog signaling pathway in this manuscript. We demonstrate that hedgehog pathway is indispensable for the establishment of male external genitalia characteristics. Sonic hedgehog is expressed in the urethral plate epithelium, and its signal is mediated through glioblastoma 2 (Gli2) in the mesenchyme. The expression level of the sexually dimorphic genes is decreased in the glioblastoma 2 mutant embryos, suggesting that hedgehog signal is likely to facilitate the masculinization processes by affecting the androgen responsiveness. In addition, a conditional mutation of Sonic hedgehog at the sexual differentiation stage leads to abnormal male external genitalia development. The current study identified hedgehog signaling pathway as a key factor not only for initial development but also for sexually dimorphic development of the external genitalia in coordination with androgen signaling.

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