Somites form along the embryonic axis by sequential segmentation from the presomitic mesoderm (PSM) and differentiate into the segmented vertebral column as well as other unsegmented tissues. Somites are thought to form via the intersection of two activities known as the clock and the wavefront. Previous work has suggested that fibroblast growth factor (FGF) activity may be the wavefront signal, which maintains the PSM in an undifferentiated state. However, it is unclear which (if any) of the FGFs expressed in the PSM comprise this activity, as removal of any one gene is insufficient to disrupt early somitogenesis. Here we show that when both Fgf4 and Fgf8 are deleted in the PSM, expression of most PSM genes is absent, including cycling genes, WNT pathway genes, and markers of undifferentiated PSM. Significantly, markers of nascent somite cell fate expand throughout the PSM, demonstrating the premature differentiation of this entire tissue, a highly unusual phenotype indicative of the loss of wavefront activity. When WNT signaling is restored in mutants, PSM progenitor markers are partially restored but premature differentiation of the PSM still occurs, demonstrating that FGF signaling operates independently of WNT signaling. This study provides genetic evidence that FGFs are the wavefront signal and identifies the specific FGF ligands that encode this activity. Furthermore, these data show that FGF action maintains WNT signaling, and that both signaling pathways are required in parallel to maintain PSM progenitor tissue.genetic redundancy | Spry | T-Cre | axis extension | paraxial mesoderm
Serotonin (5HT) plays major roles in the physiological regulation of many behavioral processes, including sleep, feeding, and mood, but the genetic mechanisms by which serotonergic neurons arise during development are poorly understood. In the present study, we have investigated the development of serotonergic neurons in the zebrafish. Neurons exhibiting 5HT-immunoreactivity (5HT-IR) are detected from 45 h postfertilization (hpf) in the ventral hindbrain raphe, the hypothalamus, pineal organ, and pretectal area. Tryptophan hydroxylases encode rate-limiting enzymes that function in the synthesis of 5HT. As part of this study, we cloned and analyzed a novel zebrafish tph gene named tphR. Unlike two other zebrafish tph genes (tphD1 and tphD2), tphR is expressed in serotonergic raphe neurons, similar to tph genes in mammalian species. tphR is also expressed in the pineal organ where it is likely to be involved in the pathway leading to synthesis
One of the two crystal structures of the arm-dimerization domain determined in the absence of arbinose fails to show the arm, whereas the other structure does show it. The two structures lead to different pictures for the regulatory behavior of the arms. Trypsin digestion, fluorescence anisotropy, and NMR experiments presented here were designed to resolve the issue and show that in arm-dimerization domain, the arms are structured, although differently, in the presence and absence of arabinose. The arms have also been shown to interact with the DNA binding domains of AraC by their requirement for the immobilization of the DNA binding domains that is necessary for DNA looping and repression. The binding of arabinose has been shown to release the DNA binding domains and looping ceases. The picture resulting from the new experiments and the crystal structures of the arm-dimerization domain is that in the absence of arabinose, the arm adopts one structure on the dimerization domain and that the DNA binding domain then binds to this complex. Upon binding arabinose, the arm restructures and as a result, no longer serves as a gasket between the DNA binding domain and dimerization domain. The DNA binding domain is then released, subject only to the constraints imposed by the flexible linker connecting it to dimerization domain, and the protein relocates on the DNA and activates transcription.
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