cdx4/lacZ and cdx2/lacZ protein gradients formed by decay during gastrulation in the mouse

Gaunt, Stephen J.; Drage, Deborah; Trubshaw, Richard C.

doi:10.1387/ijdb.052021sg

Cited by 34 publications

(41 citation statements)

References 32 publications

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“…Cdx gene expression then transiently persists in the neuroectoderm, including in pre-migratory NCCs (Coutaud and Pilon, 2013). At the onset of neurulation (E8.5), this is exemplified by a posterior (high) to anterior (low) gradient of transcript and protein distribution in the developing spinal cord, with an anterior limit of expression around the level of the hindbrain/spinal cord boundary set by Cdx1 (Beck et al, 1995;Gamer and Wright, 1993;Gaunt et al, 2003Gaunt et al, , 2005Meyer and Gruss, 1993). This anterior limit of expression is not permanent as it regresses caudally concomitantly with axial elongation.…”

Section: Introductionmentioning

confidence: 99%

A direct role for murine Cdx proteins in the trunk neural crest-gene regulatory network

et al. 2016

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Numerous studies in chordates and arthropods currently indicate that Cdx proteins have a major ancestral role in the organization of posthead tissues. In urochordate embryos, Cdx loss-of-function has been shown to impair axial elongation, neural tube (NT) closure and pigment cell development. Intriguingly, in contrast to axial elongation and NT closure, a Cdx role in neural crest (NC)-derived melanocyte/ pigment cell development has not been reported in any other chordate species. To address this, we generated a new conditional pan-Cdx functional knockdown mouse model that circumvents Cdx functional redundancy as well as the early embryonic lethality of Cdx mutants. Through directed inhibition in the neuroectoderm, we provide in vivo evidence that murine Cdx proteins impact melanocyte and enteric nervous system development by, at least in part, directly controlling the expression of the key early regulators of NC ontogenesis Pax3, Msx1 and Foxd3. Our work thus reveals a novel role for Cdx proteins at the top of the trunk NC gene regulatory network in the mouse, which appears to have been inherited from their ancestral ortholog.

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Section: Introductionmentioning

confidence: 99%

A direct role for murine Cdx proteins in the trunk neural crest-gene regulatory network

et al. 2016

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“…Posterior shifts of vertebral types are commonly described as posterior-to-anterior homeotic transformations (van den Akker et al, 2002). The Cdx proteins are distributed as posterior-to-anterior concentration gradients along the developing embryo (Beck et al, 1995;Gamer and Wright, 1993;Meyer and Gruss, 1993), and evidence from Cdx/lacZ reporter mice has shown that these gradients may form by decay of Cdx protein in cells once they leave the region of intense Cdx gene expression within the primitive streak/tailbud (Gaunt et al, 2003;Gaunt et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Increased Cdx protein dose effects upon axial patterning in transgenic lines of mice

2008

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To investigate the link between Cdx protein concentration and axial patterning in embryos, we made lines of mice OE1, OE2 and OE4 that overexpress each of the Cdx genes Cdx1, Cdx2 and Cdx4, respectively. The lines carry Cdx transgenes under the transcriptional control of their own promoter/enhancer elements. Transgenic embryos show Cdx transcription at 8.5 to 8.7 days within normal spatial domains for Cdx expression (primitive streak/tailbud), yet, overall, they contain elevated levels of Cdx proteins. Increased doses of Cdx proteins result in homeotic shifts in vertebral types along most of the vertebral column, with transformations being most obvious within the cervical region. Most of the shifts are anterior-to-posterior transformations and the anterior limits of these are commonly skull/vertebra 1 (v1) for OE1, v1/v2 for OE2 and v7 for OE4. OE embryos display anterior shifts in the expression of a Hoxa7/lacZ reporter within neural, paraxial and lateral plate mesoderm tissues. Hoxa7/lacZ expression commences at the normal time in OE1 and OE4 embryos. OE2 embryos display a forward shift in the gradient of Cdx2 protein along the axis, suggesting that a Cdx morphogen gradient model could account, at least in part, for the homeotic shifts in vertebral types. OE mice display additional defects: forelimb deficiencies in OE1, multiple tail axes, vertebral mis-alignments and axial truncations in OE2.

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“…Fig. 1C shows that Cdx1/lacZ reporter is stimulated by RA, whereas Cdx2/lacZ and Cdx4/lacZ, both expressed in transgenic mice (Gaunt et al, 2005), show little evidence of stimulation.…”

Section:     -Galactosidase Chemiluminescence To Detect Cdx1 Repmentioning

confidence: 98%

“…Construct #3 has the Cdx1 component of construct #1 spliced in-frame to luciferase. Cdx2/lacZ and Cdx4/lacZ reporters are constructs 5 and 1 described earlier (Gaunt et al, 2005).…”

Section: Plasmidsmentioning

confidence: 99%

Origins of Cdx1 regulatory elements suggest roles in vertebrate evolution

Gaunt¹,

Paul²

2011

Int. J. Dev. Biol.

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Cdx1, an upstream regulator of Hox genes, is best characterized for its homeotic effects upon the developing axial skeleton, particularly in the neck. It responds to retinoic acid (RA) in both mouse embryos and embryonal carcinoma (EC) cells. By use of     -galactosidase chemiluminescence, we show that a mouse Cdx1/lacZ reporter expressed in P19 EC cells responds to RA by the combined activities of an intron retinoic acid response element (RARE) and an upstream RARE. In contrast, a chicken Cdx1/lacZ reporter responds only by activity of the intron RARE. Database analyses upon Cdx1 from twenty three vertebrate species reveal that the intron RARE is structurally conserved in amniotes (eutherian mammals, marsupials, birds and Anole lizard), but not in Xenopus or fish. The upstream RARE is structurally conserved only in eutherian mammals. We conclude that the intron RARE originated at around the amphibian/amniote division, and the upstream RARE appeared around the marsupial/eutherian mammal division. In view of the site of action of Cdx1, we propose that acquisition of the intron RARE may have facilitated the substantial changes that occurred in the neck and anterior thorax at the advent of the amniotes. We present evidence that Cdx1 is also a developmental regulator of the female urogenital system, and we suggest that acquisition of the upstream RARE may have contributed to morphological divergence of marsupial and eutherian mammals.

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cdx4/lacZ and cdx2/lacZ protein gradients formed by decay during gastrulation in the mouse

Cited by 34 publications

References 32 publications

A direct role for murine Cdx proteins in the trunk neural crest-gene regulatory network

A direct role for murine Cdx proteins in the trunk neural crest-gene regulatory network

Increased Cdx protein dose effects upon axial patterning in transgenic lines of mice

Origins of Cdx1 regulatory elements suggest roles in vertebrate evolution

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