Conserved regulatory elements establish the dynamic expression of Rpx/HesxI in early vertebrate development

Chou, Shen Ju; Hermesz, Edit; Hatta, Toshihisa; Feltner, Doug; El‐Hodiri, Heithem M.; Jamrich, Milan; Mahon, Kathleen

doi:10.1016/j.ydbio.2005.12.053

Cited by 29 publications

(22 citation statements)

References 37 publications

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“…LHX1 binds the dTAAT and pTAAT elements (referred to hereafter as the dp region) of the Hesx1 locus (Fig. 5D) (Chou et al, 2006). As expected, ChIP-PCR in P19 cells using the anti-HA antibody and the LHX1-HA expression constructs confirmed the binding of LHX1 to the dp region of the Hesx1 locus (Fig.…”

Section: Loss Of Lhx1 Disrupts the Formation Of Anterior Midline Tissuessupporting

confidence: 78%

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Context-specific function of the LIM homeobox 1 transcription factor in head formation of the mouse embryo

Fossat

Jones

et al. 2015

Development

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Lhx1 encodes a LIM homeobox transcription factor that is expressed in the primitive streak, mesoderm and anterior mesendoderm of the mouse embryo. Using a conditional Lhx1 flox mutation and three different Cre deleters, we demonstrated that LHX1 is required in the anterior mesendoderm, but not in the mesoderm, for formation of the head. LHX1 enables the morphogenetic movement of cells that accompanies the formation of the anterior mesendoderm, in part through regulation of Pcdh7 expression. LHX1 also regulates, in the anterior mesendoderm, the transcription of genes encoding negative regulators of WNT signalling, such as Dkk1, Hesx1, Cer1 and Gsc. Embryos carrying mutations in Pcdh7, generated using CRISPRCas9 technology, and embryos without Lhx1 function specifically in the anterior mesendoderm displayed head defects that partially phenocopied the truncation defects of Lhx1-null mutants. Therefore, disruption of Lhx1-dependent movement of the anterior mesendoderm cells and failure to modulate WNT signalling both resulted in the truncation of head structures. Compound mutants of Lhx1, Dkk1 and Ctnnb1 show an enhanced head truncation phenotype, pointing to a functional link between LHX1 transcriptional activity and the regulation of WNT signalling. Collectively, these results provide comprehensive insight into the context-specific function of LHX1 in head formation: LHX1 enables the formation of the anterior mesendoderm that is instrumental for mediating the inductive interaction with the anterior neuroectoderm and LHX1 also regulates the expression of factors in the signalling cascade that modulate the level of WNT activity.

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Section: Loss Of Lhx1 Disrupts the Formation Of Anterior Midline Tissuessupporting

confidence: 78%

“…Loss of Lhx1 in the AME results in the downregulation of genes that encode WNT signalling antagonists, such as Dkk1, Hesx1, Cer1 and Gsc. Hesx1 is a direct target of LHX1 (Chou et al, 2006) and Hesx1…”

Section: Discussionmentioning

confidence: 99%

Context-specific function of the LIM homeobox 1 transcription factor in head formation of the mouse embryo

Fossat

Jones

et al. 2015

Development

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“…S7 in the supplementary material). It has also been reported that Lhx1 and Lhx3 activate the Hesx/Rpx/Xanf gene through their common enhancers in mice and Xenopus (Chou et al, 2006). Thus, Lhx3 could function in the organizer, similar to Lhx1.…”

Section: An Evolutionary Scenario For the Gastrula Organizermentioning

confidence: 93%

Evolutionary origins of blastoporal expression and organizer activity of the vertebrate gastrula organizer genelhx1and its ancient metazoan paraloglhx3

et al. 2009

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Expression of the LIM homeobox gene lhx1 (lim1) is specific to the vertebrate gastrula organizer. Lhx1 functions as a transcriptional regulatory core protein to exert 'organizer' activity in Xenopus embryos. Its ancient paralog, lhx3 (lim3), is expressed around the blastopore in amphioxus and ascidian, but not vertebrate, gastrulae. These two genes are thus implicated in organizer evolution, and we addressed the evolutionary origins of their blastoporal expression and organizer activity. Gene expression analysis of organisms ranging from cnidarians to chordates suggests that blastoporal expression has its evolutionary root in or before the ancestral eumetazoan for lhx1, but possibly in the ancestral chordate for lhx3, and that in the ascidian lineage, blastoporal expression of lhx1 ceased, whereas endodermal expression of lhx3 has persisted. Analysis of organizer activity using Xenopus embryos suggests that a co-factor of LIM homeodomain proteins, Ldb, has a conserved function in eumetazoans to activate Lhx1, but that Lhx1 acquired organizer activity in the bilaterian lineage, Lhx3 acquired organizer activity in the deuterostome lineage and ascidian Lhx3 acquired a specific transactivation domain to confer organizer activity on this molecule. Knockdown analysis using cnidarian embryos suggests that Lhx1 is required for chordin expression in the blastoporal region. These data suggest that Lhx1 has been playing fundamental roles in the blastoporal region since the ancestral eumetazoan arose, that it contributed as an 'original organizer gene' to the evolution of the vertebrate gastrula organizer, and that Lhx3 could be involved in the establishment of organizer gene networks.

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“…2) was antigen VE-1 (Rosenquist and Martin, 1995), providing clues that the EVE is molecularly regionalized. Then, a number of gene products, mainly transcription factors that are also found in other tissues, such as the node and/or anterior neural plate, started to be found in both chick primary hypoblast and mouse EVE, including the homeobox genes Otx2 (Acampora et al, 2009;Albazerchi et al, 2007;Bally-Cuif et al, 1995;Kurokawa et al, 2010;PereaGomez et al, 2001), Hex (Yatskievych et al, 1999) and Hesx1/Rpx (Chou et al, 2006;Thomas and Beddington, 1996), and others encoding transcription factors of the GATA and SOX families (Artus et al, 2011).…”

Section: Gene Expression In the Hypoblast And Vementioning

confidence: 99%

The hypoblast (visceral endoderm): an evo-devo perspective

2012

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SummaryWhen amniotes appeared during evolution, embryos freed themselves from intracellular nutrition; development slowed, the mid-blastula transition was lost and maternal components became less important for polarity. Extra-embryonic tissues emerged to provide nutrition and other innovations. One such tissue, the hypoblast (visceral endoderm in mouse), acquired a role in fixing the body plan: it controls epiblast cell movements leading to primitive streak formation, generating bilateral symmetry. It also transiently induces expression of pre-neural markers in the epiblast, which also contributes to delay streak formation. After gastrulation, the hypoblast might protect prospective forebrain cells from caudalizing signals. These functions separate mesendodermal and neuroectodermal domains by protecting cells against being caught up in the movements of gastrulation.

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Conserved regulatory elements establish the dynamic expression of Rpx/HesxI in early vertebrate development

Cited by 29 publications

References 37 publications

Context-specific function of the LIM homeobox 1 transcription factor in head formation of the mouse embryo

Context-specific function of the LIM homeobox 1 transcription factor in head formation of the mouse embryo

Evolutionary origins of blastoporal expression and organizer activity of the vertebrate gastrula organizer genelhx1and its ancient metazoan paraloglhx3

The hypoblast (visceral endoderm): an evo-devo perspective

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