Morphological boundary forms by a novel inductive event mediated by Lunatic fringe and Notch during somitic segmentation

Development ◽  
2002 ◽  
Vol 129 (15) ◽  
pp. 3633-3644 ◽  
Author(s):  
Yuki Sato ◽  
Kunio Yasuda ◽  
Yoshiko Takahashi
Keyword(s):  
Molecular Mechanisms ◽  
Active Form ◽  
Border Region ◽  
Paraxial Mesoderm ◽  
Posterior Border ◽  
In Ovo ◽  
Tissue Separation ◽  
Lunatic Fringe ◽  
In Ovo Electroporation ◽  
Flanking Regions

Boundary formation plays a central role in differentiating the flanking regions that give rise to discrete tissues and organs during early development. We have studied mechanisms by which a morphological boundary and tissue separation are regulated by examining chicken somite segmentation as a model system. By transplanting a small group of cells taken from a presumptive border into a non-segmentation site, we have found a novel inductive event where posteriorly juxtaposed cells to the next-forming border instruct the anterior cells to become separated and epithelialized. We have further studied the molecular mechanisms underlying these interactions by focusing on Lunatic fringe, a modulator of Notch signaling, which is expressed in the region of the presumptive boundary. By combining DNA in ovo electroporation and embryonic transplantation techniques we have ectopically made a sharp boundary of Lunatic fringe activity in the unsegmented paraxial mesoderm and observed a fissure formed at the interface. In addition, a constitutive active form of Notch mimics this instructive phenomenon. These suggest that the boundary-forming signals emanating from the posterior border cells are mediated by Notch, the action of which is confined to the border region by Lunatic fringe within the area where mRNAs of Notch and its ligand are broadly expressed in the presomitic mesoderm.

Engrailed defines the position of dorsal di-mesencephalic boundary by repressing diencephalic fate

Development ◽  
1999 ◽  
Vol 126 (22) ◽  
pp. 5127-5135 ◽  
Author(s):  
I. Araki ◽  
H. Nakamura
Keyword(s):  
Molecular Mechanisms ◽  
Chimeric Protein ◽  
Negative Regulator ◽  
Chick Embryos ◽  
Wild Type ◽  
In Ovo ◽  
Positive Form ◽  
In Ovo Electroporation ◽  
The Brain

Regionalization of a simple neural tube is a fundamental event during the development of central nervous system. To analyze in vivo the molecular mechanisms underlying the development of mesencephalon, we ectopically expressed Engrailed, which is expressed in developing mesencephalon, in the brain of chick embryos by in ovo electroporation. Misexpression of Engrailed caused a rostral shift of the di-mesencephalic boundary, and caused transformation of dorsal diencephalon into tectum, a derivative of dorsal mesencephalon. Ectopic Engrailed rapidly repressed Pax-6, a marker for diencephalon, which preceded the induction of mesencephalon-related genes such as Pax-2, Pax-5, Fgf8, Wnt-1 and EphrinA2. In contrast, a mutant Engrailed, En-2(F51rE), bearing mutation in EH1 domain, which has been shown to interact with a co-repressor, Groucho, did not show the phenotype induced by wild-type Engrailed. Furthermore, VP16-Engrailed chimeric protein, the dominant positive form of Engrailed, caused caudal shift of di-mesencephalic boundary and ectopic Pax-6 expression in mesencephalon. These data suggest that (1) Engrailed defines the position of dorsal di-mesencephalic boundary by directly repressing diencephalic fate, and (2) Engrailed positively regulates the expression of mesencephalon-related genes by repressing the expression of their negative regulator(s).

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.

Microarray analysis of Akt1 activation in transgenic mouse hearts reveals transcript expression profiles associated with compensatory hypertrophy and failure

2006 ◽  
Vol 27 (2) ◽  
pp. 156-170 ◽  
Author(s):  
Stephan Schiekofer ◽  
Ichiro Shiojima ◽  
Kaori Sato ◽  
Gennaro Galasso ◽  
Yuichi Oshima ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Molecular Mechanisms ◽  
Interstitial Fibrosis ◽  
Expression Profiles ◽  
Active Form ◽  
Heart Tissue ◽  
Compensatory Hypertrophy ◽  
Transcript Expression ◽  
Heart Size

To investigate molecular mechanisms involved in the development of cardiac hypertrophy and heart failure, we developed a tetracycline-regulated transgenic system to conditionally switch a constitutively active form of the Akt1 protein kinase on or off in the adult heart. Short-term activation (2 wk) of Akt1 resulted in completely reversible hypertrophy with maintained contractility. In contrast, chronic Akt1 activation (6 wk) induced extensive cardiac hypertrophy, severe contractile dysfunction, and massive interstitial fibrosis. The focus of this study was to create a transcript expression profile of the heart as it undergoes reversible Akt1-mediated hypertrophy and during the transition from compensated hypertrophy to heart failure. Heart tissue was analyzed before transgene induction, 2 wk after transgene induction, 2 wk of transgene induction followed by 2 days of repression, 6 wk after transgene induction, and 6 wk of transgene induction followed by 2 wk of repression. Acute overexpression of Akt1 (2 wk) leads to changes in the expression of 826 transcripts relative to noninduced hearts, whereas chronic induction (6 wk) led to changes in the expression of 1,611, of which 65% represented transcripts that were regulated during the pathological phase of heart growth. Another set of genes identified was uniquely regulated during heart regression but not growth, indicating that nonoverlapping transcription programs participate in the processes of cardiac hypertrophy and atrophy. These data define the gene regulatory programs downstream of Akt that control heart size and contribute to the transition from compensatory hypertrophy to heart failure.

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