Hex: a homeobox gene revealing peri-implantation asymmetry in the mouse embryo and an early transient marker of endothelial cell precursors

Development ◽  
1998 ◽  
Vol 125 (1) ◽  
pp. 85-94 ◽  
Author(s):  
P.Q. Thomas ◽  
A. Brown ◽  
R.S. Beddington
Keyword(s):  
Endothelial Cell ◽  
Mouse Embryo ◽  
Expression Patterns ◽  
Homeobox Gene ◽  
Definitive Endoderm ◽  
Visceral Endoderm ◽  
Primitive Endoderm ◽  
Mouse Development ◽  
Expression Domain ◽  
Early Marker

The divergent homeobox gene Hex exhibits three notable expression patterns during early mouse development. Initially Hex is expressed in the primitive endoderm of the implanting blastocyst but by 5.5 dpc its transcripts are present only in a small patch of visceral endoderm at the distal tip of the egg cylinder. Lineage analysis shows that these cells move unilaterally to assume an anterior position while continuing to express Hex. The primitive streak forms on the opposite side of the egg cylinder from this anterior Hex expression domain approximately 24 hours after the initial anterior movement of the distal visceral endoderm. Thus, Hex expression marks the earliest unequivocal molecular anteroposterior asymmetry in the mouse embryo and indicates that the anteroposterior axis of the embryo develops from conversion of a proximodistal asymmetry established in the primitive endoderm lineage. Subsequently, Hex is expressed in the earliest definitive endoderm to emerge from the streak and its expression within the gut strongly suggests that the ventral foregut is derived from the most anterior definitive endoderm and that the liver is probably the most anterior gut derivative. Hex is also an early marker of the thyroid primordium. Within the mesoderm, Hex is transiently expressed in the nascent blood islands of the visceral yolk sac and later in embryonic angioblasts and endocardium. Comparison with flk-1 (T. P. Yamaguchi et al., Development 118, 489–498, 1993) expression indicates that Hex is also an early marker of endothelial precursors but its expression in this progenitor population is much more transient than that of flk-1, being downregulated once endothelial cell differentiation commences.

flk-1, an flt-related receptor tyrosine kinase is an early marker for endothelial cell precursors

Development ◽  
1993 ◽  
Vol 118 (2) ◽  
pp. 489-498 ◽  
Author(s):  
T.P. Yamaguchi ◽  
D.J. Dumont ◽  
R.A. Conlon ◽  
M.L. Breitman ◽  
J. Rossant
Keyword(s):  
Endothelial Cell ◽  
Tyrosine Kinase ◽  
Blood Vessels ◽  
Tyrosine Kinases ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Morphological Evidence ◽  
Mouse Development ◽  
Early Marker

We have used RT-PCR to screen pluripotent murine embryonic stem cells to identify receptor tyrosine kinases (RTKs) potentially involved in the determination or differentiation of cell lineages during early mouse development. Fourteen different tyrosine kinase sequences were identified. The expression patterns of four RTKs have been examined and all are expressed in the mouse embryo during, or shortly after, gastrulation. We report here the detailed expression pattern of one such RTK, the flt-related gene flk-1. In situ hybridization analysis of the late primitive streak stage embryo revealed that flk-1 was expressed in the proximal-lateral embryonic mesoderm; tissue fated to become heart. By headfold stages, staining was confined to the endocardial cells of the heart primordia as well as to the blood islands of the visceral yolk sac and the developing allantois. Patchy, speckled staining was detected in the endothelium of all the major embryonic and extraembryonic blood vessels as they formed. During early organogenesis, expression was detected in the blood vessels of highly vascularized tissues such as the brain, liver, lungs and placenta. Since flk-1 was expressed in early mesodermal cells prior to any morphological evidence for endothelial cell differentiation (vasculogenesis), as well as in cells that form blood vessels from preexisting ones (angiogenesis), it appears to be a very early marker of endothelial cell precursors. We have previously reported that another novel RTK, designated tek, was expressed in differentiating endothelial cells. We show here that flk-1 transcripts are expressed one full embryonic day earlier than the first tek transcripts. The expression of these two RTKs appear to correlate with the specification and early differentiation of the endothelial cell lineage respectively, and therefore may play important roles in the establishment of this lineage.

The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3455-3468 ◽  
Author(s):  
Dominic P. Norris ◽  
Jane Brennan ◽  
Elizabeth K. Bikoff ◽  
Elizabeth J. Robertson
Keyword(s):  
Mouse Embryo ◽  
Late Onset ◽  
Axis Formation ◽  
Visceral Endoderm ◽  
Mouse Development ◽  
Developmental Abnormalities ◽  
Intronic Enhancer ◽  
Vertebrate Embryo ◽  
Early Mouse ◽  
Pitx2 Expression

The TGFβ-related growth factor Nodal governs anteroposterior (AP) and left-right (LR) axis formation in the vertebrate embryo. A conserved intronic enhancer (ASE), containing binding sites for the fork head transcription factor Foxh1, modulates dynamic patterns of Nodal expression during early mouse development. This enhancer is responsible for early activation of Nodal expression in the epiblast and visceral endoderm, and at later stages governs asymmetric expression during LR axis formation. We demonstrate ASE activity is strictly Foxh1 dependent. Loss of this autoregulatory enhancer eliminates transcription in the visceral endoderm and decreases Nodal expression in the epiblast, but causes surprisingly discrete developmental abnormalities. Thus lowering the level of Nodal signaling in the epiblast disrupts both orientation of the AP axis and specification of the definitive endoderm. Targeted removal of the ASE also dramatically reduces left-sided Nodal expression, but the early events controlling LR axis specification are correctly initiated. However loss of the ASE disrupts Lefty2 (Leftb) expression and causes delayed Pitx2 expression leading to late onset, relatively minor LR patterning defects. The feedback loop is thus essential for maintenance of Nodal signals that selectively regulate target gene expression in a temporally and spatially controlled fashion in the mouse embryo.

Misexpression of Cwnt8C in the mouse induces an ectopic embryonic axis and causes a truncation of the anterior neuroectoderm

Development ◽  
1997 ◽  
Vol 124 (15) ◽  
pp. 2997-3005 ◽  
Author(s):  
H. Popperl ◽  
C. Schmidt ◽  
V. Wilson ◽  
C.R. Hume ◽  
J. Dodd ◽  
...  
Keyword(s):  
Mouse Embryo ◽  
Primitive Streak ◽  
Primitive Endoderm ◽  
Morphological Examination ◽  
Expression Domain ◽  
Anterior Aspect ◽  
Beta Actin ◽  
Early Expression ◽  
Actin Promoter ◽  
Transgenic Embryos

Transgenic embryos expressing Cwnt8C under the control of the human beta-actin promoter exhibit duplicated axes or a severely dorsalised phenotype. Although the transgene was introduced into fertilised eggs all duplications occurred within a single amnion and, therefore, arose from the production of more than one primitive streak at the time of gastrulation. Morphological examination and the expression of diagnostic markers in transgenic embryos suggested that ectopic Cwnt8C expression produced only incomplete axis duplication: axes were always fused anteriorly, there was a reduction in tissue rostral to the anterior limit of the notochord, and no duplicated expression domain of the forebrain marker Hesx1 was observed. Anterior truncations were evident in dorsalised transgenic embryos containing a single axis. These results are discussed in the light of the effects of ectopic Xwnt8 in Xenopus embryos, where its early expression leads to complete axis duplication but expression after the mid-blastula transition causes anterior truncation. It is proposed that while ectopic Cwnt8C in the mouse embryo can duplicate the primitive streak and node this only produces incomplete axis duplication because specification of the anterior aspect of the axis, as opposed to maintenance of anterior character, is established by interaction with anterior primitive endoderm rather than primitive streak derivatives.

Expression patterns of vHNF1 and HNF1 homeoproteins in early postimplantation embryos suggest distinct and sequential developmental roles

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 783-797 ◽  
Author(s):  
S. Cereghini ◽  
M.O. Ott ◽  
S. Power ◽  
M. Maury
Keyword(s):  
Transcriptional Activation ◽  
Target Genes ◽  
Fetal Liver ◽  
Expression Patterns ◽  
Yolk Sac ◽  
Control Element ◽  
Visceral Endoderm ◽  
Mouse Development ◽  
F9 Cells

The homeoproteins HNF1 (LFB1/HNF1-A) and vHNF1 (LFB3/HNF1 beta) interact with an essential control element of a group of liver-specific genes. During development, these putative target genes are initially expressed in the visceral endoderm of the yolk sac and subsequently in fetal liver. To assess the possible involvement of HNF1 and/or vHNF1 as transcriptional regulators in the early steps of visceral endoderm differentiation, we have analyzed the expression pattern of both factors both in vitro during differentiation of murine F9 embryonal carcinoma cells and in vivo during early postimplantation mouse development. We show here that differentiation of F9 cells into either visceral or parietal endoderm is accompanied by a sharp induction in vHNF1 mRNA and protein. By contrast, only low levels of aberrantly sized HNF1 transcripts, but not DNA-binding protein, are found in F9 cells and its differentiated derivatives. At 6–7.5 days of gestation, high levels of vHNF1 mRNA are present in the visceral extraembryonic endoderm, which co-localize with transcripts of the transthyretin gene. HNF1 transcripts are first detected in the yolk sac roughly two embryonic days later, after the developmental onset of transcription of target genes. As development proceeds, discrepancies are observed between the level of transcripts of both vHNF1 and HNF1 and their respective nuclear binding proteins, notably in the yolk sac and embryonic kidney. In addition, we show that two alternative spliced isoforms of vHNF1 mRNA, vHNF-A and vHNF1-B, are expressed in both embryonic and adult tissues. Taken together, these data suggest that vHNF1 participates as a regulatory factor in the initial transcriptional activation of the target genes in the visceral endoderm of the yolk sac, whereas the later appearance of HNF1 could be required for maintenance of their expression. Our results also provide evidence of a posttranscriptional level of control of vHNF1 and HNF1 gene expression during development, in addition to the spatial restriction in transcription.

Vasculogenesis in the day 6.5 to 9.5 mouse embryo

Blood ◽  
2000 ◽  
Vol 95 (5) ◽  
pp. 1671-1679 ◽  
Author(s):  
Christopher J. Drake ◽  
Paul A. Fleming
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Mouse Embryo ◽  
Expression Patterns ◽  
Hematopoietic Cells ◽  
Sequential Pattern ◽  
Temporal Expression ◽  
Hematopoietic Lineage ◽  
Associated Proteins

The process of vasculogenesis was characterized in the 6.5- to 9.5-day mouse embryo and in allantoic culture by analysis of spatial and temporal expression patterns of the endothelial or hematopoietic lineage-associated proteins, TAL1, Flk1, platelet/endothelial cell adhision molecule (PECAM), CD34, VE-cadherin, and Tie2. The study establishes that: (1) TAL1 and Flk1 are coexpressed in isolated mesodermal cells that give rise to endothelial cells and thus can be defined as angioblasts; (2) hematopoietic cells of blood islands express TAL1, but not Flk1; (3) vasculogenesis in the embryo proper is initiated by mesoderm fated to give rise to the endocardium; (4) the maturation/morphogenesis of blood vessels can be defined in terms of a sequential pattern of expression in which TAL1 and Flk1 are expressed first followed by PECAM, CD34, VE-cadherin, and later Tie2; and (5) TAL1 expression is down-regulated in endothelial cells of mature vessels.

scholarly journals The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2433-2445 ◽  
Author(s):  
J.P. Martinez Barbera ◽  
M. Clements ◽  
P. Thomas ◽  
T. Rodriguez ◽  
D. Meloy ◽  
...  
Keyword(s):  
Normal Development ◽  
Embryonic Stem ◽  
Homeobox Gene ◽  
Definitive Endoderm ◽  
Visceral Endoderm ◽  
Wild Type ◽  
Zona Limitans Intrathalamica ◽  
Ventral Thalamus ◽  
Septum Transversum ◽  
Early Mouse

The homeobox gene Hex is expressed in the anterior visceral endoderm (AVE) and rostral definitive endoderm of early mouse embryos. Later, Hex transcripts are detected in liver, thyroid and endothelial precursor cells. A null mutation was introduced into the Hex locus by homologous recombination in embryonic stem cells. Hex mutant embryos exhibit varying degrees of anterior truncation as well as liver and thyroid dysplasia. The liver diverticulum is formed but migration of hepatocytes into the septum transversum fails to occur. Development of the thyroid is arrested at the thyroid bud stage at 9.5 dpc. Brain defects are restricted to the rostral forebrain and have a caudal limit at the zona limitans intrathalamica, the boundary between dorsal and ventral thalamus. Analysis of Hex(−/−) mutants at early stages shows that the prospective forebrain ectoderm is correctly induced and patterned at 7.5 days post coitum (dpc), but subsequently fails to develop. AVE markers are expressed and correctly positioned but development of rostral definitive endoderm is greatly disturbed in Hex(−/−) embryos. Chimeric embryos composed of Hex(−/−) cells developing within a wild-type visceral endoderm show forebrain defects indicating that Hex is required in the definitive endoderm. All together, these results demonstrate that Hex function is essential in definitive endoderm for normal development of the forebrain, liver and thyroid gland.

scholarly journals Patterning of the embryo: the first spatial decisions in the life of a mouse

Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 815-829 ◽  
Author(s):  
Magdalena Zernicka-Goetz
Keyword(s):  
Mouse Embryo ◽  
Molecular Mechanisms ◽  
Blastocyst Stage ◽  
The Body ◽  
Axis Formation ◽  
Visceral Endoderm ◽  
Spatial Cues ◽  
Mouse Development ◽  
Animal Pole ◽  
Embryonic Polarity

Although in most species the polarity of the embryo takes its roots from the spatial patterning of the egg, mammals were viewed as an exception. This was because the anteroposterior polarity of the mouse embryo could not be seen until gastrulation, and no developmental cues were known that could define polarity at earlier stages. Why should we now re-consider this view? While mechanisms of axis formation in mammals could, in principle, be unique, the evolutionary conservation of numerous other developmental processes raises the question of why mammals would have evolved a different way or timing of organising their embryonic polarity. Indeed, recent evidence shows that well before the onset of gastrulation, the mouse embryo initiates asymmetric patterns of gene expression in its visceral endoderm. Although this extra-embryonic tissue does not contribute to the body itself, it is involved in axis formation. Other recent work has revealed that spatial distribution of cells in the visceral endoderm can be traced back to polarity present at the blastocyst stage. These insights have raised the possibility that embryonic polarity might also originate early during development of mammalian embryos. Indeed it now appears that there are at least two spatial cues that operate in the mouse egg to shape polarity of the blastocyst. One of these is at the animal pole, which is defined by the site of female meiosis, and another is associated with the position of sperm entry. In this review I discuss these recent findings, which have led to the recognition that mouse embryos initiate development of their polarity at the earliest stages of their life. This novel perspective raises questions about the nature of cellular and molecular mechanisms that could convert developmental cues in the zygote to axes of the blastocyst, and hence into polarity of the post-implantation embryo. It also brings to light the need to understand how such mechanisms could enable early mouse development to be so regulative.

scholarly journals Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo

2009 ◽  
Vol 184 (2) ◽  
pp. 323-334 ◽  
Author(s):  
Masamichi Yamamoto ◽  
Hideyuki Beppu ◽  
Katsuyoshi Takaoka ◽  
Chikara Meno ◽  
En Li ◽  
...  
Keyword(s):  
Mouse Embryo ◽  
Early Stage ◽  
Distal Region ◽  
Bmp Signaling ◽  
Visceral Endoderm ◽  
Inverse Relation ◽  
Primitive Endoderm ◽  
Dual Roles ◽  
Morphogenetic Protein ◽  
Anterior Posterior

The anterior–posterior axis of the mouse embryo is established by formation of distal visceral endoderm (DVE) and its subsequent migration. The precise mechanism of DVE formation has remained unknown, however. Here we show that bone morphogenetic protein (BMP) signaling plays dual roles in DVE formation. BMP signaling is required at an early stage for differentiation of the primitive endoderm into the embryonic visceral endoderm (VE), whereas it inhibits DVE formation, restricting it to the distal region, at a later stage. A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal. DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal. An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling.

scholarly journals Extended expression of MaKN1 contributes to the leaf morphology in aquatic forms of Myriophyllum aquaticum

Botany ◽  
2015 ◽  
Vol 93 (9) ◽  
pp. 611-621
Author(s):  
M.D. Shafiullah ◽  
Christian R. Lacroix
Keyword(s):  
Apical Meristem ◽  
Leaf Morphology ◽  
Expression Patterns ◽  
Homeobox Gene ◽  
Leaf Primordia ◽  
Leaf Primordium ◽  
Myriophyllum Aquaticum ◽  
Knox Gene ◽  
Leaf Morphogenesis

Myriophyllum aquaticum (Vell.) Verdc. is heterophyllous in nature with highly dissected simple leaves consisting of several lobes. KNOX (KNOTTED1-LIKE HOMEOBOX) genes are believed to have played an important role in the evolution of leaf diversity. Up-regulation of KNOX during leaf primordium initiation can lead to leaf dissection in plants with simple leaves and, if overexpressed, can produce ectopic meristems on leaves. A previous study on KNOX gene expression in the aerial form of this species showed that this gene is expressed in the shoot apical meristem (SAM), as well as in leaf primordia P0 to P8. Based on these results, it was hypothesized that the prolonged expression of the MaKN1 (Myriophyllum aquaticum Knotted1-like homeobox) gene beyond P8, might play an important role in the generation of more lobes, longer lobes, and hydathode formation in the aquatic leaves of M. aquaticum. The technique of in situ hybridization was carried out using a previously sequenced 300 bp fragment of MaKN1 to determine the expression patterns of this gene in the shoot of aquatic forms of the plant. Expression patterns of MaKN1 revealed that the SAM and leaf primordia of aquatic forms of M. aquaticum at levels P0 (youngest) to P4 were distributed throughout these structures. The level of expression of this MaKN1 gene progressively became more localized to lobes in older leaf primordia (levels P5 to P12). Previous studies of aerial forms of this plant showed MaKN1 expression until P8. Our results with aquatic forms show that the highly dissected leaf morphology in aquatic forms was the result of the prolonged expression of MaKN1 beyond P8. This resulted in the formation of elongated and slightly more numerous lobes, and hydathodes in aquatic forms. These findings support the view that KNOX genes are important developmental regulators of leaf morphogenesis and have played an important role in the evolution of leaf forms in the plant kingdom.

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