Hox Targets and Cellular Functions

Sánchez‐Herrero, Ernesto

doi:10.1155/2013/738257

Cited by 29 publications

(28 citation statements)

References 305 publications

(451 reference statements)

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“…The cellular side of Hox activity Recent reviews have summarised the many different cellular functions controlled by Hox proteins, including changes in cell shape and migration, proliferation or programmed cell death and differentiation (Cerdá-Esteban and Spagnoli, 2014;Philippidou and Dasen, 2013;Sanchez-Herrero, 2013;Shah and Sukumar, 2010;Taniguchi, 2014). Here, we review phenotypes associated with Hox gene dysfunction/manipulation that provide insights, at least at the phenomenological level, into how Hox genes achieve their functions.…”

Section: An Overview Of the Hox Gene Familymentioning

confidence: 99%

“…For example, initial studies recognised the patterning functions of Hox genes, showing that they provide axial positional information and contribute to defining cellular territories and establishing boundaries. More recent work showed that Hox genes also provide contributions to organogenesis per se (Hombria and Lovegrove, 2003) through the control of a variety of cellular functions including differentiation, proliferation, migration or death (Sanchez-Herrero, 2013). Although various molecular functions have been attributed to Hox proteins, including non-transcriptional functions such as replication and translation (Miotto and Graba, 2010;Rezsohazy, 2014) (Box 1), Hox proteins are best known as transcription factors.…”

Section: Introductionmentioning

confidence: 99%

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Cellular and molecular insights into Hox protein action

et al. 2015

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Hox genes encode homeodomain transcription factors that control morphogenesis and have established functions in development and evolution. Hox proteins have remained enigmatic with regard to the molecular mechanisms that endow them with specific and diverse functions, and to the cellular functions that they control. Here, we review recent examples of Hox-controlled cellular functions that highlight their versatile and highly context-dependent activity. This provides the setting to discuss how Hox proteins control morphogenesis and organogenesis. We then summarise the molecular modalities underlying Hox protein function, in particular in light of current models of transcription factor function. Finally, we discuss how functional divergence between Hox proteins might be achieved to give rise to the many facets of their action.

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Section: An Overview Of the Hox Gene Familymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cellular and molecular insights into Hox protein action

et al. 2015

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“…One aspect of vertebrate hematopoiesis that has not been mirrored in Drosophila is the role of Hox genes. Hox genes are well known for their conserved role in body axis formation across all bilaterians [25], but also play roles in vertebrate hematopoiesis [26], autophagy [27], as well as cell proliferation, differentiation, migration and apoptosis [28]. Hox genes are transcribed in HSCs as well as lineage progenitors, while being suppressed in differentiated blood cells [29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

DrosophilaHox genes induce melanised pseudo-tumours when misexpressed in hemocytes

Ponrathnam

Mishra

2018

Preprint

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Keywords:Hemocytes melanised pseudotumours acute myeloid leukaemia leukaemia/leukemogenicity haematopoiesis Hox genes 2 Abstract:Homeotic genes are the key early determinants of cell identity along the anterior-posterior body axis across bilaterians. More recently, however, several late non-homeotic functions of hox genes have emerged in a variety of organogenesis processes, including in mammals.Being crucial factors in determining cell identity and organogenesis, the misregulation of hox genes is likely to be associated with defects in these processes. Several studies have reported misexpression of hox genes in a variety of malignancies including acute myeloid leukaemia.Considering that Drosophila is a well-established model for the study of haematopoiesis, we ectopically expressed the hox genes, Dfd, Ubx, abd-A and Abd-B, to ask if and how it will alter the process of haematopoiesis. We observed black melanised spots circulating in the viscera of the larvae and extensive lethality at during the pupal stage in these conditions. Such abnormalities are the hallmark of dysregulated haematopoiesis. We also observed an increase in blood cell number as well as their enhanced differentiation into lamellocytes. Our study opens a new possibility of addressing the function hox genes in normal and leukemogenic hematopoiesis with potential implications in downstream targets for diagnostic markers and therapy. 3 Summary: Drosophila Hox genes, when expressed in blood cells, are leukemogenic, induce cell autonomous proliferation and differentiation. This reinforces previous studies in vertebrates and allows for Hox induced leukaemia to be studied in Drosophila.

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“…One aspect of vertebrate hematopoiesis that has not been mirrored in Drosophila is the role of Hox genes. Hox genes are well known for their conserved role in body axis formation across all bilaterians 5 27 , but also play roles in vertebrate hematopoiesis 28 , autophagy 29 , as well as cell proliferation, differentiation, migration and apoptosis 30 . Hox genes are transcribed in HSCs as well as lineage progenitors, and are suppressed in differentiated blood cells [31][32][33][34][35] Overexpression models show blockages in certain stages of development, expansion of HSCs, the circulation of blast cells, etc.…”

mentioning

confidence: 99%

Drosophila Hox genes induce melanised pseudo-tumours when misexpressed in hemocytes

Ponratnam

Saini

Mishra

2020

Preprint

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Background: Hox genes are key early determinants of cell identity along the anterior-posterior body axis across bilaterians. Recently, several late non-homeotic functions of Hox genes have emerged in a variety of processes involved in organogenesis in several organisms, including mammals. Being crucial factors in determining cell identity and organogenesis, the misregulation of Hox genes is likely to be associated with defects in these processes. Several studies have reported the misexpression of Hox genes in a variety of malignancies including acute myeloid leukaemia. Methods: The Hox genes Dfd, Ubx, abd-A and Abd-B were overexpressed via the UAS-Gal4 system using Cg-Gal4, Lsp2-Gal4, He-Gal4 and HmlD3-Gal4 as specific drivers. Genetic interaction was tested by bringing overexpression lines in heterozygous mutant backgrounds of Polycomb and trithorax group factors. Larvae were visually scored for melanised bodies. Hemocytes were quantified by dissecting larvae for lymph in 4mm wells and staining nuclei with DAPI and tested for differentiation by staining them with anti-myospheroid and for proliferation with anti-PH3. Pupal lethality was carried out by letting pupae eclose and scoring those that failed after the time point. Results: Expression of Dfd, Ubx and abd-A, but not Abd-B in the hematopoietic compartment of Drosophila led to the appearance of circulating melanised bodies, and increase in cell numbers, cell-autonomous proliferation and differentiation of hemocytes. Pupal lethality and the melanised pseudo-tumor phenotype were suppressed by the mutations in Psc1 and esc2 background while polycomb group member mutations Pc1 and Su(z)123 and trithorax group member mutation TrlR85 increased the phenotype.Conclusions: Dfd, Ubx and abd-A are leukemogenic. Mutations in Polycomb and trithorax group members, which are responsible for maintaining the expression state of the Hox genes, modulate the leukemogenic phynotype. Drosophila, widely used as a model for myeloid leukemias, can serve as a testbed for Hox expression induced leukemias.

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Hox Targets and Cellular Functions

Cited by 29 publications

References 305 publications

Cellular and molecular insights into Hox protein action

Cellular and molecular insights into Hox protein action

DrosophilaHox genes induce melanised pseudo-tumours when misexpressed in hemocytes

Drosophila Hox genes induce melanised pseudo-tumours when misexpressed in hemocytes

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