FGF suppresses apoptosis and induces differentiation of fibre cells in the mouse lens

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 4383-4393 ◽  
Author(s):  
R.L. Chow ◽  
G.D. Roux ◽  
M. Roghani ◽  
M.A. Palmer ◽  
D.B. Rifkin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transgenic Mice ◽  
Dominant Negative ◽  
Fgf Receptor ◽  
Fibre Cell ◽  
Dominant Negative Form ◽  
Lens Fibre ◽  
Mouse Lens ◽  
Negative Form

To determine whether fibroblast growth factor (FGF) has a role in lens development, we have generated transgenic mice expressing a dominant-negative form of the murine FGF receptor-1 (FGFRDN) in the lens. Using the fibre cell-specific alpha A-crystallin promoter to express the FGFRDN, we have asked whether FGF is required for fibre cell differentiation. The transgenic mice display diminished differentiation of fibre cells as indicated by their reduced elongation. In addition, transgenic lenses have an unusual refractile anomaly that morphological and biochemical data show results from the apoptosis of fibre cells in the central region of the lens. These results show that lens fibre cells are dependent on FGF for their survival and differentiation, and demonstrate that growth factor deprivation in vivo can lead to apoptosis.

FGF signals are involved in the differentiation of notochord cells and mesenchyme cells of the ascidianHalocynthia roretzi

Development ◽  
2001 ◽  
Vol 128 (14) ◽  
pp. 2711-2721 ◽  
Author(s):  
Yoshie Shimauchi ◽  
Seiko D. Murakami ◽  
Nori Satoh
Keyword(s):  
Receptor Gene ◽  
Epidermal Cells ◽  
Dominant Negative ◽  
Tyrosine Kinase Domain ◽  
Fgf Receptor ◽  
Dominant Negative Form ◽  
Notochord Cells ◽  
Mesenchyme Cells ◽  
Endodermal Cells ◽  
Negative Form

Differentiation of notochord cells and mesenchyme cells of the ascidian Halocynthia roretzi requires interactions with neighboring endodermal cells and previous experiments suggest that these interactions require fibroblast growth factor (FGF). In the present study, we examined the role of FGF in these interactions by disrupting signaling using the dominant negative form of the FGF receptor. An FGF receptor gene of H. roretzi (HrFGFR) is expressed both maternally and zygotically. The maternally expressed transcript was ubiquitously distributed in fertilized eggs and in early embryos. Zygotic expression became evident by the neurula stage and transcripts were detected in epidermal cells of the posterior half of embryos. Synthetic mRNA for the dominant negative form of FGFR, in which the intracellular tyrosine kinase domain was deleted, was injected into fertilized eggs to interfere with the possible function of HrFGFR. Injected eggs cleaved and gastrulated the same as the control embryos. Analyses of the expression of differentiation markers in the experimental embryos indicated that the differentiation of epidermal cells, muscle cells and endodermal cells was not affected significantly. However, manipulated embryos showed downregulation of notochord-specific Brachyury expression and failure of notochord cell differentiation, resulting in the development of tailbud embryos with shorted tails. The expression of an actin gene that is normally expressed in mesenchyme cells was also suppressed. These results suggest that FGF signals are involved in differentiation of notochord cells and mesenchyme cells in Halocynthia embryos. Furthermore, the patterning of a neuron-specific tubulin gene expression was disturbed, suggesting that the formation of the nervous system was directly affected by disrupting FGF signals or indirectly affected due to the disruption of normal notochord formation.

scholarly journals Functional Myc-Max heterodimer is required for activation-induced apoptosis in T cell hybridomas.

1994 ◽  
Vol 180 (6) ◽  
pp. 2413-2418 ◽  
Author(s):  
R P Bissonnette ◽  
A McGahon ◽  
A Mahboubi ◽  
D R Green
Keyword(s):  
T Cell ◽  
Apoptotic Cell ◽  
Tolerance Induction ◽  
Dominant Negative ◽  
Binding Partner ◽  
Dominant Negative Form ◽  
Dominant Negative Activity ◽  
Induced Apoptosis ◽  
Negative Form

T cell hybridomas respond to activation signals by undergoing apoptotic cell death, and this is likely to represent comparable events related to tolerance induction in immature and mature T cells in vivo. Previous studies using antisense oligonucleotides implicated the c-Myc protein in the phenomenon of activation-induced apoptosis. This role for c-Myc in apoptosis is now confirmed in studies using a dominant negative form of its heterodimeric binding partner, Max, which we show here inhibits activation-induced apoptosis. Further, coexpression of a reciprocally mutant Myc protein capable of forming functional heterodimers with the mutant Max can compensate for the dominant negative activity and restore activation-induced apoptosis. These results imply that Myc promotes activation-induced apoptosis by obligatory heterodimerization with Max, and therefore, by regulating gene transcription.

scholarly journals Activin-mediated mesoderm induction requires FGF

Development ◽  
1994 ◽  
Vol 120 (2) ◽  
pp. 453-462 ◽  
Author(s):  
R.A. Cornell ◽  
D. Kimelman
Keyword(s):  
Dominant Negative ◽  
Mesoderm Induction ◽  
Fibroblast Growth ◽  
Fgf Signaling ◽  
Tgf Beta ◽  
Fgf Receptor ◽  
Basic Fgf ◽  
Dominant Negative Form ◽  
Negative Form

The early patterning of mesoderm in the Xenopus embryo requires signals from several intercellular factors, including mesoderm-inducing agents that belong to the fibroblast growth factor (FGF) and TGF-beta families. In animal hemisphere explants (animal caps), basic FGF and the TGF-beta family member activin are capable of converting pre-ectodermal cells to a mesodermal fate, although activin is much more effective at inducing dorsal and anterior mesoderm than is basic FGF. Using a dominant-negative form of the Xenopus type 1 FGF receptor, we show that an FGF signal is required for the full induction of mesoderm by activin. Animal caps isolated from embryos that have been injected with the truncated FGF receptor and cultured with activin do not extend and the induction of some genes, including cardiac actin and Xbra, is greatly diminished, while the induction of other genes, including the head organizer-specific genes gsc and Xlim-1, is less sensitive. These results are consistent with the phenotype of the truncated FGF receptor-injected embryo and imply that the activin induction of mesoderm depends on FGF, with some genes requiring a higher level of FGF signaling than others.

scholarly journals Myocardial Expression of a Dominant-Negative Form of Daxx Decreases Infarct Size and Attenuates Apoptosis in an In Vivo Mouse Model of Ischemia/Reperfusion Injury

Circulation ◽  
2007 ◽  
Vol 116 (23) ◽  
pp. 2709-2717 ◽  
Author(s):  
François Roubille ◽  
Stéphane Combes ◽  
Juani Leal-Sanchez ◽  
Christian Barrère; ◽  
Frédéric Cransac ◽  
...  
Keyword(s):  
Mouse Model ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dominant Negative ◽  
Dominant Negative Form ◽  
Negative Form

Requirement ofFoxD3-class signaling for neural crest determination inXenopus

Development ◽  
2001 ◽  
Vol 128 (13) ◽  
pp. 2525-2536 ◽  
Author(s):  
Noriaki Sasai ◽  
Kenji Mizuseki ◽  
Yoshiki Sasai
Keyword(s):  
Neural Crest ◽  
Dominant Negative ◽  
Related Factor ◽  
Embryonic Patterning ◽  
Loss Of Function ◽  
Upstream Regulator ◽  
Dominant Negative Form ◽  
Neural Crest Differentiation ◽  
Negative Form

Fox factors (winged-helix transcription factors) play important roles in early embryonic patterning. We show here that FoxD3 (Forkhead 6) regulates neural crest determination in Xenopus embryos. Expression of FoxD3 in the presumptive neural crest region starts at the late gastrula stage in a manner similar to that of Slug, and overlaps with that of Zic-r1. When overexpressed in the embryo and in ectodermal explants, FoxD3 induces expression of neural crest markers. Attenuation of FoxD3-related signaling by a dominant-negative FoxD3 construct (FoxD3delN) inhibits neural crest differentiation in vivo without suppressing the CNS marker Sox2. Interestingly, these loss-of-function phenotypes are reversed by coinjecting Slug. In animal cap explants, neural crest differentiation induced by Slug and Wnt3a is also inhibited by FoxD3delN but not by a dominant-negative form of XBF2. Loss-of-function studies using dominant-negative forms of FoxD3 and Slug indicate that Slug induction by Zic factors requires FoxD3-related signaling, and that FoxD3 and Slug have different requirements in inducing downstream neural crest markers. These data demonstrate that FoxD3 (or its closely related factor) is an essential upstream regulator of neural crest determination.

Defective thymocyte proliferation and IL-2 production in transgenic mice expressing a dominant-negative form of CREB

Nature ◽  
1996 ◽  
Vol 379 (6560) ◽  
pp. 81-85 ◽  
Author(s):  
Kevin Barton ◽  
Natarajan Muthusamy ◽  
Monchai Chanyangam ◽  
Christopher Fischer ◽  
Cynthia Clendenin ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Dominant Negative ◽  
Thymocyte Proliferation ◽  
Dominant Negative Form ◽  
Negative Form
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