Journal of Developmental Biology

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2 pages, 164 KiB

Open AccessEditorial

Special Issue “Hox Genes in Development: New Paradigms”

by Samir Merabet

J. Dev. Biol. 2022, 10(3), 34; https://doi.org/10.3390/jdb10030034 - 18 Aug 2022

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Abstract

In this Special Issue on “Hox genes in development: new paradigms”, we present a compilation of articles and reviews tackling various aspects of the Hox biology field [...] Full article

(This article belongs to the Special Issue Hox Genes in Development: New Paradigms)

Research

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13 pages, 3737 KiB

Open AccessArticle

An Evolutionary Perspective on Hox Binding Site Preferences in Two Different Tissues

by Laura Folkendt, Ingrid Lohmann and Katrin Domsch

J. Dev. Biol. 2021, 9(4), 57; https://doi.org/10.3390/jdb9040057 - 13 Dec 2021

Cited by 3 | Viewed by 2997

Abstract

Transcription factor (TF) networks define the precise development of multicellular organisms. While many studies focused on TFs expressed in specific cell types to elucidate their contribution to cell specification and differentiation, it is less understood how broadly expressed TFs perform their precise functions [...] Read more.

Transcription factor (TF) networks define the precise development of multicellular organisms. While many studies focused on TFs expressed in specific cell types to elucidate their contribution to cell specification and differentiation, it is less understood how broadly expressed TFs perform their precise functions in the different cellular contexts. To uncover differences that could explain tissue-specific functions of such TFs, we analyzed here genomic chromatin interactions of the broadly expressed Drosophila Hox TF Ultrabithorax (Ubx) in the mesodermal and neuronal tissues using bioinformatics. Our investigations showed that Ubx preferentially interacts with multiple yet tissue-specific chromatin sites in putative regulatory regions of genes in both tissues. Importantly, we found the classical Hox/Ubx DNA binding motif to be enriched only among the neuronal Ubx chromatin interactions, whereas a novel Ubx-like motif with rather low predicted Hox affinities was identified among the regions bound by Ubx in the mesoderm. Finally, our analysis revealed that tissues-specific Ubx chromatin sites are also different with regards to the distribution of active and repressive histone marks. Based on our data, we propose that the tissue-related differences in Ubx binding behavior could be a result of the emergence of the mesoderm as a new germ layer in triploblastic animals, which might have required the Hox TFs to relax their binding specificity. Full article

(This article belongs to the Special Issue Hox Genes in Development: New Paradigms)

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9 pages, 1335 KiB

Open AccessFeature PaperArticle

Molecular Characterization of HOXA2 and HOXA3 Binding Properties

by Joshua Mallen, Manisha Kalsan, Peyman Zarrineh, Laure Bridoux, Shandar Ahmad and Nicoletta Bobola

J. Dev. Biol. 2021, 9(4), 55; https://doi.org/10.3390/jdb9040055 - 3 Dec 2021

Cited by 2 | Viewed by 2763

Abstract

The highly conserved HOX homeodomain (HD) transcription factors (TFs) establish the identity of different body parts along the antero–posterior axis of bilaterian animals. Segment diversification and the morphogenesis of different structures is achieved by generating precise patterns of HOX expression along the antero–posterior [...] Read more.

The highly conserved HOX homeodomain (HD) transcription factors (TFs) establish the identity of different body parts along the antero–posterior axis of bilaterian animals. Segment diversification and the morphogenesis of different structures is achieved by generating precise patterns of HOX expression along the antero–posterior axis and by the ability of different HOX TFs to instruct unique and specific transcriptional programs. However, HOX binding properties in vitro, characterised by the recognition of similar AT-rich binding sequences, do not account for the ability of different HOX to instruct segment-specific transcriptional programs. To address this problem, we previously compared HOXA2 and HOXA3 binding in vivo. Here, we explore if sequence motif enrichments observed in vivo are explained by binding affinities in vitro. Unexpectedly, we found that the highest enriched motif in HOXA2 peaks was not recognised by HOXA2 in vitro, highlighting the importance of investigating HOX binding in its physiological context. We also report the ability of HOXA2 and HOXA3 to heterodimerise, which may have functional consequences for the HOX patterning function in vivo. Full article

(This article belongs to the Special Issue Hox Genes in Development: New Paradigms)

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8 pages, 2501 KiB

Open AccessCommunication

Maternal Transcripts of Hox Genes Are Found in Oocytes of Platynereis dumerilii (Annelida, Nereididae)

by Georgy P. Maslakov, Nikita S. Kulishkin, Alina A. Surkova and Milana A. Kulakova

J. Dev. Biol. 2021, 9(3), 37; https://doi.org/10.3390/jdb9030037 - 4 Sep 2021

Cited by 6 | Viewed by 2869

Abstract

Hox genes are some of the best studied developmental control genes. In the overwhelming majority of bilateral animals, these genes are sequentially activated along the main body axis during the establishment of the ground plane, i.e., at the moment of gastrulation. Their activation [...] Read more.

Hox genes are some of the best studied developmental control genes. In the overwhelming majority of bilateral animals, these genes are sequentially activated along the main body axis during the establishment of the ground plane, i.e., at the moment of gastrulation. Their activation is necessary for the correct differentiation of cell lines, but at the same time it reduces the level of stemness. That is why the chromatin of Hox loci in the pre-gastrulating embryo is in a bivalent state. It carries both repressive and permissive epigenetic markers at H3 histone residues, leading to transcriptional repression. There is a paradox that maternal RNAs, and in some cases the proteins of the Hox genes, are present in oocytes and preimplantation embryos in mammals. Their functions should be different from the zygotic ones and have not been studied to date. Our object is the errant annelid Platynereis dumerilii. This model is convenient for studying new functions and mechanisms of regulation of Hox genes, because it is incomparably simpler than laboratory vertebrates. Using a standard RT-PCR on cDNA template which was obtained by reverse transcription using random primers, we found that maternal transcripts of almost all Hox genes are present in unfertilized oocytes of worm. We assessed the localization of these transcripts using WMISH. Full article

(This article belongs to the Special Issue Hox Genes in Development: New Paradigms)

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Review

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9 pages, 554 KiB

Open AccessReview

Micromanagement of Drosophila Post-Embryonic Development by Hox Genes

by Alexandra D. Buffry and Alistair P. McGregor

J. Dev. Biol. 2022, 10(1), 13; https://doi.org/10.3390/jdb10010013 - 18 Feb 2022

Cited by 5 | Viewed by 3588

Abstract

Hox genes function early in development to determine regional identity in animals. Consequently, the loss or gain of Hox gene expression can change this identity and cause homeotic transformations. Over 20 years ago, it was observed that the role of Hox genes in [...] Read more.

Hox genes function early in development to determine regional identity in animals. Consequently, the loss or gain of Hox gene expression can change this identity and cause homeotic transformations. Over 20 years ago, it was observed that the role of Hox genes in patterning animal body plans involves the fine-scale regulation of cell fate and identity during development, playing the role of ‘micromanagers’ as proposed by Michael Akam in key perspective papers. Therefore, as well as specifying where structures develop on animal bodies, Hox genes can help to precisely sculpt their morphology. Here, we review work that has provided important insights about the roles of Hox genes in influencing cell fate during post-embryonic development in Drosophila to regulate fine-scale patterning and morphology. We also explore how this is achieved through the regulation of Hox genes, specific co-factors and their complex regulation of hundreds of target genes. We argue that further investigating the regulation and roles of Hox genes in Drosophila post-embryonic development has great potential for understanding gene regulation, cell fate and phenotypic differentiation more generally. Full article

(This article belongs to the Special Issue Hox Genes in Development: New Paradigms)

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17 pages, 1632 KiB

Open AccessReview

Transcriptional Regulation and Implications for Controlling Hox Gene Expression

by Zainab Afzal and Robb Krumlauf

J. Dev. Biol. 2022, 10(1), 4; https://doi.org/10.3390/jdb10010004 - 10 Jan 2022

Cited by 15 | Viewed by 8480

Abstract

Hox genes play key roles in axial patterning and regulating the regional identity of cells and tissues in a wide variety of animals from invertebrates to vertebrates. Nested domains of Hox expression generate a combinatorial code that provides a molecular framework for specifying [...] Read more.

Hox genes play key roles in axial patterning and regulating the regional identity of cells and tissues in a wide variety of animals from invertebrates to vertebrates. Nested domains of Hox expression generate a combinatorial code that provides a molecular framework for specifying the properties of tissues along the A–P axis. Hence, it is important to understand the regulatory mechanisms that coordinately control the precise patterns of the transcription of clustered Hox genes required for their roles in development. New insights are emerging about the dynamics and molecular mechanisms governing transcriptional regulation, and there is interest in understanding how these may play a role in contributing to the regulation of the expression of the clustered Hox genes. In this review, we summarize some of the recent findings, ideas and emerging mechanisms underlying the regulation of transcription in general and consider how they may be relevant to understanding the transcriptional regulation of Hox genes. Full article

(This article belongs to the Special Issue Hox Genes in Development: New Paradigms)

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14 pages, 817 KiB

Open AccessFeature PaperReview

HOX Protein Activity Regulation by Cellular Localization

by Laure Bridoux, Françoise Gofflot and René Rezsohazy

J. Dev. Biol. 2021, 9(4), 56; https://doi.org/10.3390/jdb9040056 - 7 Dec 2021

Cited by 3 | Viewed by 2964

Abstract

While the functions of HOX genes have been and remain extensively studied in distinct model organisms from flies to mice, the molecular biology of HOX proteins remains poorly documented. In particular, the mechanisms involved in regulating the activity of HOX proteins have been [...] Read more.

While the functions of HOX genes have been and remain extensively studied in distinct model organisms from flies to mice, the molecular biology of HOX proteins remains poorly documented. In particular, the mechanisms involved in regulating the activity of HOX proteins have been poorly investigated. Nonetheless, based on data available from other well-characterized transcription factors, it can be assumed that HOX protein activity must be finely tuned in a cell-type-specific manner and in response to defined environmental cues. Indeed, records in protein–protein interaction databases or entries in post-translational modification registries clearly support that HOX proteins are the targets of multiple layers of regulation at the protein level. In this context, we review here what has been reported and what can be inferred about how the activities of HOX proteins are regulated by their intracellular distribution. Full article

(This article belongs to the Special Issue Hox Genes in Development: New Paradigms)

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21 pages, 1204 KiB

Open AccessReview

MEIS1 in Hematopoiesis and Cancer. How MEIS1-PBX Interaction Can Be Used in Therapy

by Francesco Blasi and Chiara Bruckmann

J. Dev. Biol. 2021, 9(4), 44; https://doi.org/10.3390/jdb9040044 - 13 Oct 2021

Cited by 5 | Viewed by 3400

Abstract

Recently MEIS1 emerged as a major determinant of the MLL-r leukemic phenotype. The latest and most efficient drugs effectively decrease the levels of MEIS1 in cancer cells. Together with an overview of the latest drugs developed to target MEIS1 in MLL-r leukemia, we [...] Read more.

Recently MEIS1 emerged as a major determinant of the MLL-r leukemic phenotype. The latest and most efficient drugs effectively decrease the levels of MEIS1 in cancer cells. Together with an overview of the latest drugs developed to target MEIS1 in MLL-r leukemia, we review, in detail, the role of MEIS1 in embryonic and adult hematopoiesis and suggest how a more profound knowledge of MEIS1 biochemistry can be used to design potent and effective drugs against MLL-r leukemia. In addition, we present data showing that the interaction between MEIS1 and PBX1 can be blocked efficiently and might represent a new avenue in anti-MLL-r and anti-leukemic therapy. Full article

(This article belongs to the Special Issue Hox Genes in Development: New Paradigms)

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23 pages, 967 KiB

Open AccessReview

There and Back Again: Hox Clusters Use Both DNA Strands

by Elena L. Novikova and Milana A. Kulakova

J. Dev. Biol. 2021, 9(3), 28; https://doi.org/10.3390/jdb9030028 - 15 Jul 2021

Cited by 3 | Viewed by 3082

Abstract

Bilaterian animals operate the clusters of Hox genes through a rich repertoire of diverse mechanisms. In this review, we will summarize and analyze the accumulated data concerning long non-coding RNAs (lncRNAs) that are transcribed from sense (coding) DNA strands of Hox clusters. It [...] Read more.

Bilaterian animals operate the clusters of Hox genes through a rich repertoire of diverse mechanisms. In this review, we will summarize and analyze the accumulated data concerning long non-coding RNAs (lncRNAs) that are transcribed from sense (coding) DNA strands of Hox clusters. It was shown that antisense regulatory RNAs control the work of Hox genes in cis and trans, participate in the establishment and maintenance of the epigenetic code of Hox loci, and can even serve as a source of regulatory peptides that switch cellular energetic metabolism. Moreover, these molecules can be considered as a force that consolidates the cluster into a single whole. We will discuss the examples of antisense transcription of Hox genes in well-studied systems (cell cultures, morphogenesis of vertebrates) and bear upon some interesting examples of antisense Hox RNAs in non-model Protostomia. Full article

(This article belongs to the Special Issue Hox Genes in Development: New Paradigms)

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15 pages, 2877 KiB

Open AccessFeature PaperReview

Physical Laws Shape Up HOX Gene Collinearity

by Spyros Papageorgiou

J. Dev. Biol. 2021, 9(2), 17; https://doi.org/10.3390/jdb9020017 - 6 May 2021

Cited by 2 | Viewed by 2749

Abstract

Hox gene collinearity (HGC) is a multi-scalar property of many animal phyla particularly important in embryogenesis. It relates entities and events occurring in Hox clusters inside the chromosome DNA and in embryonic tissues. These two entities differ in linear size by more than [...] Read more.

Hox gene collinearity (HGC) is a multi-scalar property of many animal phyla particularly important in embryogenesis. It relates entities and events occurring in Hox clusters inside the chromosome DNA and in embryonic tissues. These two entities differ in linear size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC), where the Hox genes are located in the order (Hox1, Hox2, Hox3 …) along the 3′ to 5′ direction of DNA in the genome and a corresponding sequence of ontogenetic units (E1, E2, E3, …) located along the Anterior—Posterior axis of the embryo. Expression of Hox1 occurs in E1, Hox2 in E2, Hox3 in E3, etc. Besides SC, a temporal collinearity (TC) has been also observed in many vertebrates. According to TC, first Hox1 is expressed in E1; later, Hox2 is expressed in E2, followed by Hox3 in E3, etc. Lately, doubt has been raised about whether TC really exists. A biophysical model (BM) was formulated and tested during the last 20 years. According to BM, physical forces are created which pull the Hox genes one after the other, driving them to a transcription factory domain where they are transcribed. The existing experimental data support this BM description. Symmetry is a physical–mathematical property of matter that was explored in depth by Noether who formulated a ground-breaking theory (NT) that applies to all sizes of matter. NT may be applied to biology in order to explain the origin of HGC in animals developing not only along the A/P axis, but also to animals with circular symmetry. Full article

(This article belongs to the Special Issue Hox Genes in Development: New Paradigms)

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