A time space translation hypothesis for vertebrate axial patterning

Durston, Antony J.; Zhu, Kangshun

doi:10.1016/j.semcdb.2015.06.001

Cited by 29 publications

(48 citation statements)

References 41 publications

(115 reference statements)

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“…For example, an initial delay of HoxC8 expression results in phenocopies similar to HoxC8 null mutants [15], suggesting that correctly timed initial expression of Hox genes at earlier stages is crucial for specifying AP identities at later stages. Whereas there are also studies proposing a disconnection between Hox temporal and spatial collinearities [16, 17], our recent studies argue for an indispensable role for Hox temporal collinearity in generating spatial collinearity [11, 18]. Our research in early Xenopus development suggests that the temporally collinear expression of Hox genes serves as a timer during the formation of the A-P axis.…”

Section: Introductionmentioning

confidence: 57%

Collinear Hox-Hox interactions are involved in patterning the vertebrate anteroposterior (A-P) axis

2017

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Investigating regulation and function of the Hox genes, key regulators of positional identity in the embryo, opened a new vista in developmental biology. One of their most striking features is collinearity: the temporal and spatial orders of expression of these clustered genes each match their 3’ to 5’ order on the chromosome. Despite recent progress, the mechanisms underlying collinearity are not understood. Here we show that ectopic expression of 4 different single Hox genes predictably induces and represses expression of others, leading to development of different predictable specific sections of the body axis. We use ectopic expression in wild-type and noggin—dorsalised (Hox-free) Xenopus embryos, to show that two Hox-Hox interactions are important. Posterior induction (induction of posterior Hox genes by anterior ones: PI), drives Hox temporal collinearity (Hox timer), which itself drives anteroposterior (A-P) patterning. Posterior prevalence (repression of anterior Hox genes by posterior ones: PP) is important in translating temporal to spatial collinearity. We thus demonstrate for the first time that two collinear Hox interactions are important for vertebrate axial patterning. These findings considerably extend and clarify earlier work suggesting the existence and importance of PP and PI, and provide a major new insight into genesis of the body axis.

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Section: Introductionmentioning

confidence: 57%

Collinear Hox-Hox interactions are involved in patterning the vertebrate anteroposterior (A-P) axis

2017

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“…Organizer molecules that may control cell polarity, adhesion or motility have not been explored with the same rigor. Similarly, while it is known that temporal changes in tissues surrounding the dorsal blastopore is associated with anterior-posterior (AP) patterning of the body axis (Slack and Tannahill, 1992; Durston and Zhu, 2015), factors that may link AP cell fates and distinct motile cell behaviors are not well scrutinized. To acquire a more detailed understanding of how cells destined to differentiate into specific lineages also adopt particular motile behaviors, we performed RNA-seq analyses in this study to gain insight into distinct transcriptomes in tissues with defined cell fates and migratory patterns.…”

Section: Discussionmentioning

confidence: 99%

Identification of new regulators of embryonic patterning and morphogenesis in Xenopus gastrulae by RNA sequencing

Popov

Kwon

Crossman

et al. 2017

Developmental Biology

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During early vertebrate embryogenesis, cell fate specification is often coupled with cell acquisition of specific adhesive, polar and/or motile behaviors. In Xenopus gastrulae, tissues fated to form different axial structures display distinct motility. The cells in the early organizer move collectively and directionally toward the animal pole and contribute to anterior mesendoderm, whereas the dorsal and the ventral-posterior trunk tissues surrounding the blastopore of mid-gastrula embryos undergo convergent extension and convergent thickening movements, respectively. While factors regulating cell lineage specification have been described in some detail, the molecular machinery that controls cell motility is not understood in depth. To gain insight into the gene battery that regulates both cell fates and motility in particular embryonic tissues, we performed RNA sequencing (RNA-seq) to investigate differentially expressed genes in the early organizer, the dorsal and the ventral marginal zone of Xenopus gastrulae. We uncovered many known signaling and transcription factors that have been reported to play roles in embryonic patterning during gastrulation. We also identified many uncharacterized genes as well as genes that encoded extracellular matrix (ECM) proteins or potential regulators of actin cytoskeleton. Co-expression of a selected subset of the differentially expressed genes with activin in animal caps revealed that they had distinct ability to block activin-induced animal cap elongation. Most of these factors did not interfere with mesodermal induction by activin, but an ECM protein, EFEMP2, inhibited activin signaling and acted downstream of the activated type I receptor. By focusing on a secreted protein kinase PKDCC1, we showed with overexpression and knockdown experiments that PKDCC1 regulated gastrulation movements as well as anterior neural patterning during early Xenopus development. Overall, our studies identify many differentially expressed signaling and cytoskeleton regulators in different embryonic regions of Xenopus gastrulae and imply their functions in regulating cell fates and/or behaviors during gastrulation.

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“…the repression of hoxc4 and c5 by hoxc6), and posterior induction (the induction of posterior Hox genes by anterior ones, e.g., the induction of hoxc8,9, and 10-13 by hoxc6) (reviewed in Ref. 4). Interestingly, hoxa6 and b6 were also downregulated by hoxc6 LOF, suggesting interactions also exist among Hox clusters.…”

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confidence: 99%

“…In part this difference may reflect the fact that, in Xenopus but possibly not in mouse, expression of the other later hox6 paralogues depends on the earlier hoxc6. The most important difference however is likely to be that, while the entire axis is specified early in anamniotes like Xenopus, 4 the mouse A-P axis is specified over a much longer period and is dependent on axial growth. 10,11 The striking hoxc6 LOF phenotype in Xenopus emphasizes the importance of collinear Hox-Hox interactions in Hox collinearity.…”

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confidence: 99%

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Hoxc6 loss of function truncates the main body axis in Xenopus

2017

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During animal development, the formation of the anteriorposterior (A-P) axis is of fundamental importance, because it sets the stage for subsequent tissue differentiation and organogenesis. Patterning along the A-P axis requires the expression of Hox genes to specify positional information. 1 In mammals, these genes are organized into 4 chromosomal (HOXA-D) clusters containing 39 members. Equivalent genes within each cluster are divided into 13 paralogous groups (HOX1-13). During A-P patterning, Hox genes are expressed in a temporal sequence that matches their 3' to 5' arrangement on the chromosome (temporal collinearity). 2This precisely controlled timing in Hox gene expression potentially provides a timing mechanism for the formation of A-P structures, that are laid down from head to tail progressively during early development.3 Actually, Hox temporal collinearity is prerequisite for establishing the correct spatial pattern of Hox gene expression, 4 which also reflects their 3' to 5' order on the chromosome (spatial collinearity). Therefore, not only is temporal collinearity an interesting feature of Hox genes, it is also likely to play a crucial role in A-P patterning. Nonetheless, the nature of Hox temporal collinearity has yet to be fully elucidated.In an attempt to understand what drives the Hox timer (temporal collinearity), we did hoxc6 loss of function (LOF) in the Xenopus by injection of a hoxc6 morpholino (MO) (5'-ATTCATATCTTCTCCTTTACCTGCC-3') at 2-cell or 4-cell stage. The effectiveness and specificity of this MO have been demonstrated previously.5 Remarkably, injection of 60ng hoxc6 MO cut off the posterior part of the axis completely, whereas injection of the same amount of control MO did not affect axis formation (Fig. 1A). Consistent with the phenotype, we observed that the expression domains of krox-20, a rhombomere marker, and otx-2, a midbrain marker, expanded posteriorly (Fig. 1B).We then asked: why did hoxc6 LOF give such a severe developmental consequence? To answer this question, we examined the expression of all the 9 genes in the HOXC cluster (hoxc4, 5, 6, 8, 9, 10, 11, 12 and13) and all the 3 genes in the hox6 paralogous group (hoxa6, b6 and c6) at st.26 (Fig. 1C). In hoxc6 LOF embryos, hoxc6 was downregulated by 50%, confirming the morpholino worked. The downregulation of hoxc6 was accompanied by upregulation of hoxc4 and c5 and by downregulation of most Hox genes that are posterior to hoxc6 in the HOXC cluster. These results indicate 2 previously identified types of Hox interactions within the HOXC cluster: posterior prevalence (the repression or antagonism of anterior Hox genes by posterior ones, e.g. the repression of hoxc4 and c5 by hoxc6), and posterior induction (the induction of posterior Hox genes by anterior ones, e.g., the induction of hoxc8,9, and 10-13 by hoxc6) (reviewed in Ref.4). Interestingly, hoxa6 and b6 were also downregulated by hoxc6 LOF, suggesting interactions also exist among Hox clusters. This explains why Hox genes from other clusters (e.g., hoxd3, a5, and d...

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A time space translation hypothesis for vertebrate axial patterning

Cited by 29 publications

References 41 publications

Collinear Hox-Hox interactions are involved in patterning the vertebrate anteroposterior (A-P) axis

Collinear Hox-Hox interactions are involved in patterning the vertebrate anteroposterior (A-P) axis

Identification of new regulators of embryonic patterning and morphogenesis in Xenopus gastrulae by RNA sequencing

Hoxc6 loss of function truncates the main body axis in Xenopus

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