The Notch ligand, X-Delta-2, mediates segmentation of the paraxial mesoderm in Xenopus embryos

Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1169-1178 ◽  
Author(s):  
W.C. Jen ◽  
D. Wettstein ◽  
D. Turner ◽  
A. Chitnis ◽  
C. Kintner
Keyword(s):  
Paraxial Mesoderm ◽  
Bhlh Gene ◽  
Presomitic Mesoderm ◽  
Notch 1 ◽  
Notch Ligand ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Vertebrate Embryo ◽  
Somite Formation ◽  
Segmental Expression

Segmentation of the vertebrate embryo begins when the paraxial mesoderm is subdivided into somites, through a process that remains poorly understood. To study this process, we have characterized X-Delta-2, which encodes the second Xenopus homolog of Drosophila Delta. Strikingly, X-Delta-2 is expressed within the presomitic mesoderm in a set of stripes that corresponds to prospective somitic boundaries, suggesting that Notch signaling within this region establishes a segmental prepattern prior to somitogenesis. To test this idea, we introduced antimorphic forms of X-Delta-2 and Xenopus Suppressor of Hairless (X-Su(H)) into embryos, and assayed the effects of these antimorphs on somite formation. In embryos expressing these antimorphs, the paraxial mesoderm differentiated normally into somitic tissue, but failed to segment properly. Both antimorphs also disrupted the segmental expression of X-Delta-2 and Hairy2A, a basic helix-loop-helix (bHLH) gene, within the presomitic mesoderm. These observations suggest that X-Delta-2, via X-Notch-1, plays a role in segmentation, by mediating cell-cell interactions that underlie the formation of a segmental prepattern prior to somitogenesis.

her1, a zebrafish pair-rule like gene, acts downstream of notch signalling to control somite development

Development ◽  
1999 ◽  
Vol 126 (13) ◽  
pp. 3005-3014 ◽  
Author(s):  
C. Takke ◽  
J.A. Campos-Ortega
Keyword(s):  
Active Form ◽  
Notch Signalling ◽  
Paraxial Mesoderm ◽  
Presomitic Mesoderm ◽  
Essentially Normal ◽  
Early Embryos ◽  
Somite Formation ◽  
Genes Encoding ◽  
Ectopic Activation ◽  
Pair Rule

During vertebrate embryonic development, the paraxial mesoderm becomes subdivided into metameric units known as somites. In the zebrafish embryo, genes encoding homologues of the proteins of the Drosophila Notch signalling pathway are expressed in the presomitic mesoderm and expression is maintained in a segmental pattern during somitogenesis. This expression pattern suggests a role for these genes during somite development. We misexpressed various zebrafish genes of this group by injecting mRNA into early embryos. RNA encoding a constitutively active form of notch1a (notch1a-intra) and a truncated variant of deltaD [deltaD(Pst)], as well as transcripts of deltaC and deltaD, the hairy-E(spl) homologues her1 and her4, and groucho2 were tested for their effects on somite formation, myogenesis and on the pattern of transcription of putative downstream genes. In embryos injected with any of these RNAs, with the exception of groucho2 RNA, the paraxial mesoderm differentiated normally into somitic tissue, but failed to segment correctly. Activation of notch results in ectopic activation of her1 and her4. This misregulation of the expression of her genes might be causally related to the observed mesodermal defects, as her1 and her4 mRNA injections led to effects similar to those seen with notch1a-intra. deltaC and deltaD seem to function after subdivision of the presomitic mesoderm, since the her gene transcription pattern in the presomitic mesoderm remains essentially normal after misexpression of delta genes. Whereas notch signalling alone apparently does not affect myogenesis, zebrafish groucho2 is involved in differentiation of mesodermal derivatives.

scholarly journals Zebrafish Mesp family genes, mesp-a and mesp-b are segmentally expressed in the presomitic mesoderm, and Mesp-b confers the anterior identity to the developing somites

Development ◽  
2000 ◽  
Vol 127 (8) ◽  
pp. 1691-1702 ◽  
Author(s):  
A. Sawada ◽  
A. Fritz ◽  
Y. Jiang ◽  
A. Yamamoto ◽  
K. Yamasu ◽  
...  
Keyword(s):  
Fibroblast Growth Factor Receptor ◽  
Ectopic Expression ◽  
Growth Factor Receptor ◽  
Paraxial Mesoderm ◽  
Signalling Pathways ◽  
Fibroblast Growth ◽  
Presomitic Mesoderm ◽  
Receptor Signalling ◽  
Vertebrate Embryo ◽  
Bhlh Transcription Factors

Segmentation of a vertebrate embryo begins with the subdivision of the paraxial mesoderm into somites through a not-well-understood process. Recent studies provided evidence that the Notch-Delta and the FGFR (fibroblast growth factor receptor) signalling pathways are required for segmentation. In addition, the Mesp family of bHLH transcription factors have been implicated in establishing a segmental prepattern in the presomitic mesoderm. In this study, we have characterized zebrafish mesp-a and mesp-b genes that are closely related to Mesp family genes in other vertebrates. During gastrulation, only mesp-a is expressed in the paraxial mesoderm at the blastoderm margin. During the segmentation period, both genes are segmentally expressed in one to three stripes in the anterior parts of somite primordia. In fused somites (fss) embryos, in which all early somite boundary formation is blocked, initial mesp-a expression at the gastrula stage remains intact, but the expression of mesp-a and mesp-b is not detected during the segmentation period. This suggests that these genes are downstream targets of fss at the segmentation stage. Comparison with her1 expression (Muller, M., von Weizsacker, E. and Campos-Ortega, J. A. (1996) Development 122, 2071–2078) suggests that, like her1, mesp genes are not expressed in primordia of the first several somites. Furthermore, we found that zebrafish her1 expression oscillates in the presomitic mesoderm. The her1 stripe, which first appears in the tailbud region, moves in a caudal to rostral direction, and it finally overlaps the most rostral mesp stripe. Thus, in the trunk region, both her1 and mesp transcripts are detected in every somite primordium posterior to the forming somites. Ectopic expression of Mesp-b in embryos causes a loss of the posterior identity within the somite primordium, leading to a segmentation defect. These embryos show a reduction in expression of the posterior genes, myoD and notch5, with uniform expression of the anterior genes, FGFR1, papc and notch6. These observations suggest that zebrafish mesp genes are involved in anteroposterior specification within the presumptive somites, by regulating the essential signalling pathways mediated by Notch-Delta and FGFR.

Thylacine 1 is expressed segmentally within the paraxial mesoderm of the Xenopus embryo and interacts with the Notch pathway

Development ◽  
1998 ◽  
Vol 125 (11) ◽  
pp. 2041-2051 ◽  
Author(s):  
D.B. Sparrow ◽  
W.C. Jen ◽  
S. Kotecha ◽  
N. Towers ◽  
C. Kintner ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Ectopic Expression ◽  
Notch Pathway ◽  
Notch Signalling ◽  
Xenopus Embryo ◽  
Paraxial Mesoderm ◽  
Marker Genes ◽  
Transcription Activator ◽  
Presomitic Mesoderm ◽  
Helix Loop Helix

The presomitic mesoderm of vertebrates undergoes a process of segmentation in which cell-cell interactions mediated by the Notch family of receptors and their associated ligands are involved. The vertebrate homologues of Drosophila Δ are expressed in a dynamic, segmental pattern within the presomitic mesoderm, and alterations in the function of these genes leads to a perturbed pattern of somite segmentation. In this study we have characterised Thylacine 1 which encodes a basic helix-loop-helix class transcription activator. Expression of Thylacine is restricted to the presomitic mesoderm, localising to the anterior half of several somitomeres in register with domains of X-Delta-2 expression. Ectopic expression of Thylacine in embryos causes segmentation defects similar to those seen in embryos in which Notch signalling is altered, and these embryos also show severe disruption in the expression patterns of the marker genes X-Delta-2 and X-ESR5 within the presomitic mesoderm. Finally, the expression of Thylacine is altered in embryos when Notch signalling is perturbed. These observations suggest strongly that Thylacine 1 has a role in the segmentation pathway of the Xenopus embryo, by interacting with the Notch signalling pathway.

The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation

Development ◽  
2000 ◽  
Vol 127 (13) ◽  
pp. 2933-2943 ◽  
Author(s):  
S. Bae ◽  
Y. Bessho ◽  
M. Hojo ◽  
R. Kageyama
Keyword(s):  
Cell Differentiation ◽  
Neuronal Differentiation ◽  
Rod Photoreceptor ◽  
Bhlh Gene ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Differentiated Cells ◽  
Loop Region ◽  
The Family ◽  
Enhancer Of Split

We have isolated the basic helix-loop-helix (bHLH) gene Hes6, a novel member of the family of mammalian homologues of Drosophila hairy and Enhancer of split. Hes6 is expressed by both undifferentiated and differentiated cells, unlike Hes1, which is expressed only by the former cells. Hes6 alone does not bind to the DNA but suppresses Hes1 from repressing transcription. In addition, Hes6 suppresses Hes1 from inhibiting Mash1-E47 heterodimer and thereby enables Mash1 and E47 to upregulate transcription in the presence of Hes1. Furthermore, misexpression of Hes6 with retrovirus in the developing retina promotes rod photoreceptor differentiation, like Mash1, in sharp contrast to Hes1, which inhibits cell differentiation. These results suggest that Hes6 is an inhibitor of Hes1, supports Mash1 activity and promotes cell differentiation. Mutation analysis revealed that Hes1- and Hes6-specific functions are, at least in part, interchangeable by alteration of the loop region, suggesting that the loop is not simply a nonfunctional spacer but plays an important role in the specific functions.

Math5 encodes a murine basic helix-loop-helix transcription factor expressed during early stages of retinal neurogenesis

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4821-4833 ◽  
Author(s):  
N.L. Brown ◽  
S. Kanekar ◽  
M.L. Vetter ◽  
P.K. Tucker ◽  
D.L. Gemza ◽  
...  
Keyword(s):  
Bipolar Cells ◽  
Dependent Manner ◽  
Bhlh Gene ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Frog Retina ◽  
Similar Dose ◽  
Bhlh Genes ◽  
Hes1 Expression ◽  
Retinal Neurogenesis

We have identified Math5, a mouse basic helix-loop-helix (bHLH) gene that is closely related to Drosophila atonal and Xenopus Xath5 and is largely restricted to the developing eye. Math5 retinal expression precedes differentiation of the first neurons and persists within progenitor cells until after birth. To position Math5 in a hierarchy of retinal development, we compared Math5 and Hes1 expression in wild-type and Pax6-deficient (Sey) embryos. Math5 expression is downregulated in Sey/+ eyes and abolished in Sey/Sey eye rudiments, whereas the bHLH gene Hes1 is upregulated in a similar dose-dependent manner. These results link Pax6 to the process of retinal neurogenesis and provide the first molecular correlate for the dosage-sensitivity of the Pax6 phenotype. During retinogenesis, Math5 is expressed significantly before NeuroD, Ngn2 or Mash1. To test whether these bHLH genes influence the fates of distinct classes of retinal neurons, we ectopically expressed Math5 and Mash1 in Xenopus retinal progenitors. Unexpectedly, lipofection of either mouse gene into the frog retina caused an increase in differentiated bipolar cells. Directed expression of Math5, but not Xath5, in Xenopus blastomeres produced an expanded retinal phenotype. We propose that Math5 acts as a proneural gene, but has properties different from its most closely related vertebrate family member, Xath5.

scholarly journals Basic Helix-Loop-Helix Transcription Factors Cooperate To Specify a Cortical Projection Neuron Identity

2007 ◽  
Vol 28 (5) ◽  
pp. 1456-1469 ◽  
Author(s):  
Pierre Mattar ◽  
Lisa Marie Langevin ◽  
Kathryn Markham ◽  
Natalia Klenin ◽  
Salma Shivji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Projection Neuron ◽  
Luciferase Assay ◽  
Bhlh Gene ◽  
Cortical Projection ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Genes ◽  
Cortical Projection Neuron

ABSTRACT Several transcription factors are essential determinants of a cortical projection neuron identity, but their mode of action (instructive versus permissive) and downstream genetic cascades remain poorly defined. Here, we demonstrate that the proneural basic helix-loop-helix (bHLH) gene Ngn2 instructs a partial cortical identity when misexpressed in ventral telencephalic progenitors, inducing ectopic marker expression in a defined temporal sequence, including early (24 h; Nscl2), intermediate (48 h; BhlhB5), and late (72 h; NeuroD, NeuroD2, Math2, and Tbr1) target genes. Strikingly, cortical gene expression was much more rapidly induced by Ngn2 in the dorsal telencephalon (within 12 to 24 h). We identify the bHLH gene Math3 as a dorsally restricted Ngn2 transcriptional target and cofactor, which synergizes with Ngn2 to accelerate target gene transcription in the cortex. Using a novel in vivo luciferase assay, we show that Ngn2 generates only ∼60% of the transcriptional drive in ventral versus dorsal telencephalic domains, an activity that is augmented by Math3, providing a mechanistic basis for regional differences in Ngn2 function. Cortical bHLH genes thus cooperate to control transcriptional strength, thereby temporally coordinating downstream gene expression.

scholarly journals Paraxis: A Basic Helix-Loop-Helix Protein Expressed in Paraxial Mesoderm and Developing Somites

1995 ◽  
Vol 168 (2) ◽  
pp. 296-306 ◽  
Author(s):  
Rob Burgess ◽  
Peter Cserjesi ◽  
Keith L. Ligon ◽  
Eric N. Olson
Keyword(s):  
Paraxial Mesoderm ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix
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