scholarly journals Fgf/MAPK signalling is a crucial positional cue in somite boundary formation

Development ◽  
2001 ◽  
Vol 128 (23) ◽  
pp. 4873-4880 ◽  
Author(s):  
Atsushi Sawada ◽  
Minori Shinya ◽  
Yun-Jin Jiang ◽  
Atsushi Kawakami ◽  
Atsushi Kuroiwa ◽  
...  
Keyword(s):  
Experimental Manipulation ◽  
Notch Signalling ◽  
Presomitic Mesoderm ◽  
Mapk Activation ◽  
Boundary Formation ◽  
Molecular Oscillator ◽  
Spatial Regulation ◽  
Mapk Signalling ◽  
Temporal And Spatial ◽  
Segmentation Point

The temporal and spatial regulation of somitogenesis requires a molecular oscillator, the segmentation clock. Through Notch signalling, the oscillation in cells is coordinated and translated into a cyclic wave of expression of hairy-related and other genes. The wave sweeps caudorostrally through the presomitic mesoderm (PSM) and finally arrests at the future segmentation point in the anterior PSM. By experimental manipulation and analyses in zebrafish somitogenesis mutants, we have found a novel component involved in this process. We report that the level of Fgf/MAPK activation (highest in the posterior PSM) serves as a positional cue within the PSM that regulates progression of the cyclic wave and thereby governs the positions of somite boundary formation.

scholarly journals Noncyclic Notch activity in the presomitic mesoderm demonstrates uncoupling of somite compartmentalization and boundary formation

2008 ◽  
Vol 22 (16) ◽  
pp. 2166-2171 ◽  
Author(s):  
J. Feller ◽  
A. Schneider ◽  
K. Schuster-Gossler ◽  
A. Gossler
Keyword(s):  
Presomitic Mesoderm ◽  
Boundary Formation ◽  
Notch Activity

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.

Eph signalling functions downstream of Val to regulate cell sorting and boundary formation in the caudal hindbrain

Development ◽  
2001 ◽  
Vol 128 (4) ◽  
pp. 571-580 ◽  
Author(s):  
J. Cooke ◽  
C. Moens ◽  
L. Roth ◽  
L. Durbin ◽  
K. Shiomi ◽  
...  
Keyword(s):  
Cell Sorting ◽  
Tyrosine Kinases ◽  
Bzip Transcription Factor ◽  
Boundary Formation ◽  
Spatial Regulation ◽  
Genetic Mosaic ◽  
Mosaic Approach ◽  
Mediate Cell ◽  
Neural Crest Migration ◽  
Mutant Cells

Rhombomeres are segmental units of the developing vertebrate hindbrain that underlie the reiterated organisation of cranial neural crest migration and neuronal differentiation. valentino (val), a zebrafish homologue of the mouse bzip transcription factor-encoding gene, kreisler, is required for segment boundary formation caudal to rhombomere 4 (r4). val is normally expressed in r5/6 and is required for cells to contribute to this region. In val(−) mutants, rX, a region one rhombomere in length and of mixed identity, lies between r4 and r7. While a number of genes involved in establishing rhombomeric identity are known, it is still largely unclear how segmental integrity is established and boundaries are formed. Members of the Eph family of receptor tyrosine kinases and their ligands, the ephrins, are candidates for functioning in rhombomere boundary formation. Indeed, expression of the receptor ephB4a coincides with val in r5/6, whilst ephrin-B2a, which encodes a ligand for EphB4a, is expressed in r4 and r7, complementary to the domain of val expression. Here we show that in val(−) embryos, ephB4a expression is downregulated and ephrin-B2a expression is upregulated between r4 and r7, indicating that Val is normally required to establish the mutually exclusive expression domains of these two genes. We show that juxtaposition of ephB4a-expressing cells and ephrin-B2a-expressing cells in the hindbrain leads to boundary formation. Loss of the normal spatial regulation of eph/ephrin expression in val mutants correlates not only with absence of boundaries but also with the inability of mutant cells to contribute to wild-type r5/6. Using a genetic mosaic approach, we show that spatially inappropriate Eph signalling underlies the repulsion of val(−) cells from r5/6. We propose that Val controls eph expression and that interactions between EphB4a and Ephrin-B2a mediate cell sorting and boundary formation in the segmenting caudal hindbrain.

scholarly journals The multi-site docking protein Grb2-associated binder 1 (Gab1) enhances interleukin-6-induced MAPK-pathway activation in an SHP2-, Grb2-, and time-dependent manner

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Hannes Bongartz ◽  
Karen Gille ◽  
Wiebke Hessenkemper ◽  
Katharina Mandel ◽  
Marc Lewitzky ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Sh2 Domain ◽  
Time Dependent ◽  
Signalling Pathways ◽  
Dependent Manner ◽  
Mapk Activation ◽  
Pathway Activation ◽  
Mapk Signalling

Abstract Background Cytokine-dependent activation of signalling pathways is tightly orchestrated. The spatiotemporal activation of signalling pathways dictates the specific physiological responses to cytokines. Dysregulated signalling accounts for neoplastic, developmental, and inflammatory diseases. Grb2-associated binder (Gab) family proteins are multi-site docking proteins, which expand cytokine-induced signal transduction in a spatial- and time-dependent manner by coordinating the recruitment of proteins involved in mitogen activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) and phosphatidyl-inositol-3-kinase (PI3K) signalling. Interaction of Gab family proteins with these signalling proteins determines strength, duration and localization of active signalling cascades. However, the underlying molecular mechanisms of signal orchestration by Gab family proteins in IL-6-induced signalling are only scarcely understood. Methods We performed kinetic analyses of interleukin-6 (IL-6)-induced MAPK activation and analysed downstream responses. We compared signalling in wild-type cells, Gab1 knock-out cells, those reconstituted to express Gab1 mutants, and cells expressing gp130 receptors or receptor mutants. Results Interleukin-6-induced MAPK pathway activation can be sub-divided into an early Gab1-independent and a subsequent Gab1-dependent phase. Early Gab1-independent MAPK activation is critical for the subsequent initiation of Gab1-dependent amplification of MAPK pathway activation and requires binding of SH2 domain-containing phosphatase 2 (SHP2) to the interleukin-6 receptor complex. Subsequent and coordinated recruitment of Grb2 and SHP2 to Gab1 is essential for Gab1-dependent amplification of IL-6-induced late MAPK pathway activation and subsequent gene expression. Conclusions Overall, we elaborated the molecular requirements for Gab1-dependent, spatiotemporal orchestration of interleukin-6-dependent MAPK signalling. We discriminated IL-6-induced Gab1-independent, early activation of MAPK signalling and Gab1-dependent, sustained activation of MAPK signalling.

PKA, Germ Cells, and Fertility

Physiology ◽  
2007 ◽  
Vol 22 (1) ◽  
pp. 40-46 ◽  
Author(s):  
Kimberly A. Burton ◽  
G. Stanley McKnight
Keyword(s):  
Sperm Motility ◽  
Germ Cells ◽  
Genetic Mutations ◽  
Spatial Regulation ◽  
Temporal And Spatial

Temporal and spatial regulation of PKA activity are essential for vigorous sperm motility and for the resumption of meiosis in oocytes, two events required for successful fertilization. Genetic mutations in mice that affect PKA signaling in germ cells lead to infertility and illustrate the importance of this pathway in mammalian reproduction.

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