Modulating Hox gene functions during animal body patterning

Pearson, Joseph C.; Lemons, Derek; McGinnis, William

doi:10.1038/nrg1726

Cited by 807 publications

(754 citation statements)

References 123 publications

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“…It is likely that, as observed in obligate paedomorphic species, this gene network is modified in different species, resulting in a distinct outcome in terms of metamorphosis. This importance of the gene regulatory cascade controlled by a relatively invariant master regulator is reminiscent of the situation observed in other cases such as eye development [with pax6 being the master gene ] or antero-posterior development of arthropods [with Hox genes being the key selector genes (Pearson et al, 2005) and more generally (Carroll et al, 2005)]. Indeed, TH-regulated gene expression pattern is highly variable from one species to another, as shown in X. laevis and the mouse (Das et al, 2006;Yen et al, 2003).…”

Section: Modulation Of Th Availabilitymentioning

confidence: 86%

The history of a developmental stage: Metamorphosis in chordates

Paris

Laudet

2008

Genesis

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Summary: Metamorphosis displays a striking diversity in chordates, a deuterostome phylum that comprises vertebrates, urochordates (tunicates), and cephalochordates (amphioxus). In anuran amphibians, the tadpole loses its tail, develops limbs, and undergoes profound changes at the behavioral, physiological, biochemical, and ecological levels. In ascidian tunicates, the tail is lost and the head tissues are drastically remodeled into the adult animal, whereas in amphioxus, the highly asymmetric larva transforms into a relatively symmetric adult. This wide diversity has led to the proposal that metamorphosis evolved several times independently in the different chordate lineages during evolution. However, the molecular mechanisms involved in metamorphosis are largely unknown outside amphibians and teleost fishes, in which metamorphosis is regulated by the thyroid hormones (TH) T 3 and T 4 binding to their receptors (thyroid hormone receptors). In this review, we compare metamorphosis in chordates and then propose a unifying definition of the larva-to-adult transition, based on the conservation of the role of THs and some of their derivatives as the main regulators of metamorphosis. According to this definition, all chordates (if not, all deuterostomes) have a homologous metamorphosis stage during their postembryonic development. The intensity and the nature of the morphological remodeling varies extensively among taxa, from drastic remodeling like in some ascidians or amphibians to more subtle events, as in mammals. genesis 46:657-672,

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Section: Modulation Of Th Availabilitymentioning

confidence: 86%

The history of a developmental stage: Metamorphosis in chordates

Paris

Laudet

2008

Genesis

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“…Hox genes encode homeodomaincontaining transcription factors that play a major role in regional specification along the A-P embryonic axis of bilateral animals (Pearson et al, 2005). Mammals and birds have 39 and 36 Hox genes, respectively, which are arranged in four clusters in the genome from the 3 0 to the 5 0 end (Duboule, 2007;Richardson et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Comparative spatiotemporal analysis of Hox gene expression in early stages of intermediate mesoderm formation

Barak

Noon

Reshef

2012

Developmental Dynamics

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Background: Hox genes are key players in AP patterning of the vertebrate body plan and are necessary for organogenesis. Several studies provide evidence for the role Hox genes play during kidney development and especially regarding metanephros initiation and formation. However, the role Hox genes play during early stages of kidney development is largely unknown. A recent study in our lab revealed the role Hoxb4 plays in conferring the competence of intermediate mesodermal cells to respond to kidney inductive signals and express early kidney regulators. Results: As a first step in understanding the role Hox genes play in setting the formation of the pronephros morphogenetic field and the expression of early regulators of kidney development, we studied in detail the expression pattern of 10 Hox genes in relation to the 6th somite axial level, the anterior sharp border of the kidney field. Despite the idea of spatial co-linearity as exemplified in the Hox gene expression pattern in late developmental stages, a very dynamic spatio-temporal expression of these genes was found in early stages. Conclusions: Since mesodermal patterning occurs at gastrula stages, the relevance of a ''Hox code'' at early stages is questioned in this study.

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“…This has important implications for the many TFs such as Hox factors (Pearson et al 2005) or TFs downstream from signaling pathways (Barolo and Posakony 2002), which are broadly expressed but regulate certain genes specifically in some tissues but not in others: we foresee that the recent increase in celltype-specific ChIP analyses will reveal specific cis-regulatory requirements and the corresponding trans-acting factors that define the regulatory state for many cell types. Because TF binding has been shown to be predictive of cell-type-specific enhancer activity (Zinzen et al 2009; see also Stark 2009; He and Sinha 2010), this will bridge the gap between the sequence, TF binding, and enhancer/CRM function and will ultimately reveal how cell-type-specific regulatory information is encoded in the DNA sequence.…”

Section: Context-specific Codes Are Shared Among Binding Sitesmentioning

confidence: 99%

“…Cell-type-specific regulatory targets and functions have indeed been observed for many broadly expressed TFs. For example, although active in many tissues, Hox TFs regulate certain genes specifically in some tissues but not in others (Pearson et al 2005). This is even more pronounced for field-specific selector genes such as scalloped (sd) (Guss et al 2001) or TFs downstream from signaling pathways, most of which are reused throughout development and regulate different genes in different contexts (Barolo and Posakony 2002;Mullen et al 2011;Trompouki et al 2011).…”

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confidence: 99%

Uncovering cis-regulatory sequence requirements for context-specific transcription factor binding

et al. 2012

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The regulation of gene expression is mediated at the transcriptional level by enhancer regions that are bound by sequence-specific transcription factors (TFs). Recent studies have shown that the in vivo binding sites of single TFs differ between developmental or cellular contexts. How this context-specific binding is encoded in the cis-regulatory DNA sequence has, however, remained unclear. We computationally dissect context-specific TF binding sites in Drosophila, Caenorhabditis elegans, mouse, and human and find distinct combinations of sequence motifs for partner factors, which are predictive and reveal specific motif requirements of individual binding sites. We predict that TF binding in the early Drosophila embryo depends on motifs for the early zygotic TFs Vielfaltig (also known as Zelda) and Tramtrack. We validate experimentally that the activity of Twist-bound enhancers and Twist binding itself depend on Vielfaltig motifs, suggesting that Vielfaltig is more generally important for early transcription. Our finding that the motif content can predict contextspecific binding and that the predictions work across different Drosophila species suggests that characteristic motif combinations are shared between sites, revealing context-specific motif codes (cis-regulatory signatures), which appear to be conserved during evolution. Taken together, this study establishes a novel approach to derive predictive cis-regulatory motif requirements for individual TF binding sites and enhancers. Importantly, the method is generally applicable across different cell types and organisms to elucidate cis-regulatory sequence determinants and the corresponding trans-acting factors from the increasing number of tissue-and cell-type-specific TF binding studies.

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Modulating Hox gene functions during animal body patterning

Cited by 807 publications

References 123 publications

The history of a developmental stage: Metamorphosis in chordates

The history of a developmental stage: Metamorphosis in chordates

Comparative spatiotemporal analysis of Hox gene expression in early stages of intermediate mesoderm formation

Uncovering cis-regulatory sequence requirements for context-specific transcription factor binding

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