Region-specific Etv2 ablation revealed the critical origin of hemogenic capacity from Hox6-positive caudal-lateral primitive mesoderm
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Abstract:
Hematopoietic cells (HPCs) develop from hemogenic endothelial cells (ECs), a specialized type of ECs undergoing hematopoietic transition. However, the mesoderm origin for hemogenic ECs or HPCs has not been clarified. To examine the origin for hemogenic mesoderm, we inactivated Etv2, a master regulator for EC/HPC commitment, in specific regions. Region-specific Etv2 ablation in early mesoderm caused local EC differentiation block, resulting in the loss of specific vascular beds without compensatory migration of residual ECs into avascular area. This feature of local EC/HPC differentiation block was correlated to the hemogenic potential of each mesoderm subset. We found that caudal-lateral mesoderm of E7.5-8.5 embryos represent the pre-committed population critical for generating hemogenic ECs. Etv2 ablation in caudal-lateral mesoderm by Hoxb6 Cre or Hoxb6CreER transgene affected vitelline plexus formation and intra-aortic hematopoietic clusters. In differentiated embryonic stem cells, this mesoderm subset marked by Hoxb6-lateral mesoderm promoter showed enriched T lymphopoietic potential among Flk-1(+) cells, which could be regarded as a characteristic for definitive HPCs. These findings indicate that critical mesoderm precursors possibly for definitive type hemogenic ECs are regionally specified in primitive mesoderm, suggesting that Hoxb6(+) caudal-lateral mesoderm represents the critical source of HPCs, which are potentially useful to enrich definitive HPCs from embryonic stem cells.Keywords:
Lateral plate mesoderm
Intermediate mesoderm
Paraxial mesoderm
Germ layer
Intermediate mesoderm
Nodal signaling
Paraxial mesoderm
Lateral plate mesoderm
Primitive streak
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Abstract Summary: Structure and developmental expression are described for amphioxus AmphiVent, a homolog of vertebrate Vent genes. In amphioxus, AmphiVent ‐expressing ventral mesoderm arises at midneurula by outgrowth from the paraxial mesoderm, but in vertebrates, Vent ‐expressing ventral mesoderm originates earlier, at the gastrula stage. In other embryonic tissues (nascent paraxial mesoderm, neural plate, endoderm, and tailbud), AmphiVent and its vertebrate homologs are expressed in similar spatiotemporal domains, indicating conservation of many Vent gene functions during chordate evolution. The ventral mesoderm evidently develops precociously in vertebrates because their relatively large embryos probably require an early and extensive deployment of the mesoderm‐derived circulatory system. The vertebrate ventral mesoderm, in spite of its strikingly early advent, still resembles the nascent ventral mesoderm of amphioxus in expressing Vent homologs. This coincidence may indicate that Vent homologs in vertebrates and amphioxus play comparable roles in ventral mesoderm specification. genesis 29:172–179, 2001. © 2001 Wiley‐Liss, Inc.
Paraxial mesoderm
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Lateral plate mesoderm
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The gene schmalspur is involved in the Nodal signalling pathway to maintain the expression of nodal genes during zebrafish development. Mutants for nodal-related genes show a partial loss of axial mesoderm, which is also defective in embryos lacking maternal and zigotic expression of schmalspur. We have generated double mutants of schmalspur with other genes responsible for mesoderm formation and have analyzed the phenotype and the genetic interactions by whole-mount in situ hybridization. In addition, cellular transplant experiments were carried out to determine how schmalspur functions in mesoderm formation. Our results show a close genetic interaction of schmalspur with the T-box genes notail and spadetail, since the axial and paraxial mesoderm of these double mutants were strongly affected, and a non-cell autonomous function for schmalspur in mesoderm formation.
Paraxial mesoderm
Intermediate mesoderm
Lateral plate mesoderm
Nodal signaling
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Paraxial mesoderm
Intermediate mesoderm
Lateral plate mesoderm
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ABSTRACT Newly formed somites or unsegmented paraxial mesoderm (UPM) have been cultured either in isolation or with adjacent structures to investigate the influence of these tissues on myogenic differentiation in mammals. The extent of differentiation was easily and accurately quantified by counting the number of β-galactosidase-positive cells, since mesodermal tissues had been isolated from transgenic mice that carry the n-lacZ gene under the transcriptional control of a myosin light chain promoter, restricting expression to striated muscle. The results obtained showed that axial structures are necessary to promote differentiation of paraxial mesoderm, in agreement with previous observations. However, it also appeared that the influence of axial structures could be replaced by dorsolateral tissues, adjacent to the paraxial mesoderm. To elucidate which of these tissues exerts this positive effect, we cultured the paraxial mesoderm with a variety of adjacent structures, either adherent to the mesoderm or recombined in vitro. The results of these experiments indicated that the dorsal ectoderm exerts a positive influence on myogenesis but only if left in physical proximity to it. In contrast, lateral mesoderm delays the positive effect of the ectoderm (and has no effect on its own) suggesting that this tissue produces an inhibitory signal. To investigate whether axial structures and dorsal ectoderm induce myogenesis through common or separate pathways, we dissected the medial half of the unsegmented paraxial mesoderm and cultured it with the adjacent neural tube. We also cultured the lateral half of the unsegmented paraxial mesoderm with adjacent ectoderm. The induction of the myogenic regulatory factors myf-5 and MyoD was monitored by double staining of cultured cells with antibodies against MyoD and β-galactosidase since the tissues were isolated from mouse embryos that carry n-lacZ targeted to the myf-5 gene, so that myf-5-expressing cells could be easily identified by either histochemical or immunocytochemical staining for β-galactosidase. After 1 day in culture myogenic cells from the medial half expressed myf-5 but not MyoD, while myogenic cells from the lateral half expressed MyoD but not myf-5. By the next day in vitro, however, most myogenic cells expressed both gene products. These data suggest that the neural tube activates myogenesis in the medial half of paraxial mesoderm through a myf-5-dependent pathway, while the dorsal ectoderm activates myogenesis through a MyoDdependent pathway. The possible developmental significance of these observations is discussed and a model of myogenic determination in mammals is proposed.
Paraxial mesoderm
PAX3
Intermediate mesoderm
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Intermediate mesoderm
Lateral plate mesoderm
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Primitive streak
Paraxial mesoderm
Notochord
Intermediate mesoderm
Lateral plate mesoderm
Brachyury
Nodal signaling
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The apical ectodermal ridge (AER) is a specialized thickening of the distal limb ectoderm, and its signals are known to support limb morphogenesis. The expression of a homeobox gene, Msx1 , in the distal limb mesoderm depends on signals from the AER. In the present paper it is reported that Msx1 expression in the distal mesoderm is necessary for the transfer of AER signals in chick limb buds. Interruption of AER‐mesoderm interaction by insertion of a thick filter led to the inhibition of pattern specification in the mesoderm just under the filter. In such cases, the expression of Msx1 disappeared in the mesoderm under the filter, suggesting that AER is able to signal over short ranges. In advanced limb buds, Msx1 is also expressed in the proximal mesoderm under the anterior ectoderm. However, it was found that a grafted antero‐proximal mesoderm shows no inhibitory effects on pattern specification of the host mesoderm, as is the case with the distal mesoderm. On the other hand, grafted mesoderms without potent Msx1 re‐expression, even underneath AER, disturbed normal limb development. In such cases, the expression of Msx1 disappeared in the mesoderm under the grafts, whereas Fgf‐8 expression was maintained in the AER above the graft. These results indicate that the expression of Msx1 in the mesoderm is important for the transfer of AER signals.
Apical ectodermal ridge
Intermediate mesoderm
Limb development
Lateral plate mesoderm
Limb bud
Paraxial mesoderm
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Intermediate mesoderm
Lateral plate mesoderm
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Paraxial mesoderm
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