A Drosophila protein related to the human zinc finger transcription factor PRDII/MBPI/HIV-EP1 is required for dpp signaling

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3393-3403 ◽  
Author(s):  
K. Staehling-Hampton ◽  
A.S. Laughon ◽  
F.M. Hoffmann
Keyword(s):  
Signal Transduction ◽  
Transcription Factor ◽  
Cell Fate ◽  
Related Factor ◽  
Homeodomain Protein ◽  
Tgf Beta ◽  
Wing Vein ◽  
Mesoderm Cell ◽  
Visceral Mesoderm ◽  
Vein Formation

Little is known about the signal transduction pathways by which cells respond to mammalian TGF-beta s or to decapentaplegic (dpp), a Drosophila TGF-beta-related factor. Here we describe the genetic and molecular characterization of Drosophila schnurri (shn), a putative transcription factor implicated in dpp signaling. The shn protein has eight zinc fingers and is related to a human transcription factor, PRDII/MBPI/HIV-EP1, that binds to nuclear factor-kappa B-binding sites and activates transcription from the HIV long terminal repeat (LTR). shn mRNA is expressed in a dynamic pattern in the embryo that includes most of the known target tissues of dpp, including the dorsal blastoderm, the mesodermal germlayer and parasegments 4 and 7 of the midgut. Mutations in shn affect several developmental processes regulated by dpp including induction of visceral mesoderm cell fate, dorsal/ventral patterning of the lateral ectoderm and wing vein formation. Absence of shn function blocks the expanded expression of the homeodomain protein bagpipe in the embryonic mesoderm caused by ectopic dpp expression, illustrating a requirement for shn function downstream of dpp action. We conclude that shn function is critical for cells to respond properly to dpp and propose that shn protein is the first identified downstream component of the signal transduction pathway used by dpp and its receptors.

The Drosophila decapentaplegic and short gastrulation genes function antagonistically during adult wing vein development

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 4033-4044 ◽  
Author(s):  
K. Yu ◽  
M.A. Sturtevant ◽  
B. Biehs ◽  
V. Francois ◽  
R.W. Padgett ◽  
...  
Keyword(s):  
Cell Fate ◽  
Early Embryo ◽  
Common Mechanism ◽  
Tgf Beta ◽  
Wing Vein ◽  
Vein Formation ◽  
Adult Wing ◽  
Invertebrate Development ◽  
Pupal Wing ◽  
Development Analysis

TGF-beta-related signaling pathways play diverse roles during vertebrate and invertebrate development. A common mechanism for regulating the activity of TGF-beta family members is inhibition by extracellular antagonists. Recently, the Drosophila short gastrulation (sog) gene was shown to encode a predicted diffusible factor which antagonizes signaling mediated by the TGF-beta-like Decapentaplegic (Dpp) pathway in the early blastoderm embryo. sog and dpp, which are among the earliest zygotic genes to be activated, are expressed in complementary dorsal-ventral domains. The opposing actions of sog and dpp in the early embryo have been highly conserved during evolution as their vertebrate counterparts, chordin and BMP-4, function homologously to define neural versus non-neural ectoderm in Xenopus. Here we exploit the genetically sensitive adult wing vein pattern to investigate the generality of the antagonistic relationship between sog and dpp. We show that dpp is expressed in vein primordia during pupal wing development and functions to promote vein formation. In contrast, sog is expressed in complementary intervein cells and suppresses vein formation. sog and dpp function during the same phenocritical periods (i.e. 16–28 hours after pupariation) to influence the vein versus intervein cell fate choice. The conflicting activities of dpp and sog are also revealed by antagonistic dosage-sensitive interactions between these two genes during vein development. Analysis of vein and intervein marker expression in dpp and sog mutant wings suggests that dpp promotes vein fates indirectly by activating the vein gene rhomboid (rho), and that sog functions by blocking an autoactivating Dpp feedback loop. These data support the view that Sog is a dedicated Dpp antagonist.

scholarly journals Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Elliot A Perens ◽  
Zayra V Garavito-Aguilar ◽  
Gina P Guio-Vega ◽  
Karen T Peña ◽  
Yocheved L Schindler ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Zinc Finger ◽  
Kidney Development ◽  
Bhlh Transcription Factor ◽  
Lateral Boundary ◽  
Zinc Finger Transcription Factor ◽  
Cell Fate Decisions ◽  
Intermediate Mesoderm ◽  
Vein Formation

Proper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidney by restricting IM dimensions. The IM is expanded in zebrafish hand2 mutants and is diminished when hand2 is overexpressed. Within the posterior mesoderm, hand2 is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, and hand2 promotes venous development while inhibiting IM formation at this interface. Furthermore, hand2 and the co-expressed zinc-finger transcription factor osr1 have functionally antagonistic influences on kidney development. Together, our data suggest that hand2 functions in opposition to osr1 to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM.

scholarly journals Hand2 Inhibits Kidney Specification While Promoting Vein Formation Within the Posterior Mesoderm

2016 ◽  
Author(s):  
Elliot A. Perens ◽  
Zayra V. Garavito-Aguilar ◽  
Gina P. Guio-Vega ◽  
Karen T. Peña ◽  
Yocheved L. Schindler ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Zinc Finger ◽  
Kidney Development ◽  
Bhlh Transcription Factor ◽  
Lateral Boundary ◽  
Zinc Finger Transcription Factor ◽  
Cell Fate Decisions ◽  
Intermediate Mesoderm ◽  
Vein Formation

AbstractProper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidneyby restricting IM dimensions. The IM is expanded in zebrafish hand2 mutants and is diminished when hand2 is overexpressed. Within the posterior mesoderm, hand2 is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, and hand2 promotes venous development while inhibiting IM formation at this interface. Furthermore, hand2 and the co-expressed zinc-finger transcription factor osr1 have functionally antagonistic influences on kidney development. Together, our data suggest that hand2 functions in opposition to osr1 to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM.IMPACT STATEMENTThe Hand2 transcription factor regulates the dimensions of the kidney by controlling cell fate decisions at the interface between organ fields.

scholarly journals osr1 couples intermediate mesoderm cell fate with temporal dynamics of vessel progenitor cell differentiation

Development ◽  
2021 ◽  
Author(s):  
Elliot A. Perens ◽  
Jessyka T. Diaz ◽  
Agathe Quesnel ◽  
Amjad Askary ◽  
J. Gage Crump ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Temporal Dynamics ◽  
Bhlh Transcription Factor ◽  
Transcriptional Regulatory Networks ◽  
Mesoderm Cell ◽  
Intermediate Mesoderm ◽  
Transcriptional Regulatory ◽  
Mutant Phenotypes

Transcriptional regulatory networks refine gene expression boundaries to define the dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and neighboring vessel progenitors are poorly understood. Here, we delineate roles for the zinc finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafish osr1 mutants display decreased IM formation and premature emergence of lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss of hand2 partially suppresses osr1 mutant phenotypes. hand2 and osr1 are expressed together in the posterior mesoderm, but osr1 expression decreases dramatically prior to LVP emergence. Overexpressing osr1 during this timeframe inhibits LVP development while enhancing IM formation and can rescue the osr1 mutant phenotype. Together, our data demonstrate that osr1 modulates the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels of osr1 and hand2 expression is essential to demarcate the kidney and vessel progenitor territories.

Mothers against dpp encodes a conserved cytoplasmic protein required in DPP/TGF-beta responsive cells

Development ◽  
1996 ◽  
Vol 122 (7) ◽  
pp. 2099-2108 ◽  
Author(s):  
S.J. Newfeld ◽  
E.H. Chartoff ◽  
J.M. Graff ◽  
D.A. Melton ◽  
W.M. Gelbart
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Essential Element ◽  
Transduction Pathway ◽  
Tgf Beta ◽  
Hsp70 Promoter ◽  
Visceral Mesoderm ◽  
Immunohistochemical Studies ◽  
Midgut Development ◽  
In Cells

The proteins necessary for signal transduction in cells responding to ligands of the TGF-beta family are largely unknown. We have previously identified Mad (Mothers against dpp), a gene that interacts with the TGF-beta family member encoded by decapentaplegic (dpp) in Drosophila. Assay of Mad's role in the DPP-dependent events of embryonic midgut development demonstrates that Mad is required for any response of the visceral mesoderm or endoderm to DPP signals from the visceral mesoderm. Replacement of the normal DPP promoter with a heterologous (hsp70) promoter fails to restore DPP-dependent responses in Mad mutant midguts. Experiments utilizing Mad transgenes regulated by tissue-specific promoters show that MAD is required specifically in cells responding to DPP. Immunohistochemical studies localize MAD to the cytoplasm in all tissues examined. Experiments in Xenopus embryos demonstrate that Drosophila MAD can function in the signaling pathway of BMP-4, a vertebrate homolog of dpp. Based on these results, we propose that Mad is a highly conserved and essential element of the DPP signal transduction pathway.

scholarly journals Distinct roles and requirements for Ras pathway signaling in visceral versus somatic muscle founder specification

2018 ◽  
Author(s):  
Yiyun Zhou ◽  
Sarah E. Popadowski ◽  
Emily Deustchman ◽  
Marc S. Halfon
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Somatic Muscle ◽  
Cell Specification ◽  
Ets Transcription Factors ◽  
Ras Pathway ◽  
Signaling Specificity ◽  
Visceral Mesoderm ◽  
Ras Effectors

ABSTRACTPleiotropic signaling pathways must somehow engender specific cellular responses. In the Drosophila mesoderm, Ras pathway signaling specifies muscle founder cells from among the broader population of myoblasts. For somatic muscles, this is an inductive process mediated by the ETS-domain downstream Ras effectors Pointed and Aop (Yan). We demonstrate here that for the circular visceral muscles, despite superficial similarities, a significantly different specification mechanism is at work. Not only is visceral founder cell specification not dependent on Pointed or Aop, but Ras pathway signaling in its entirety can be bypassed. Our results show that de-repression, not activation, is the predominant role of Ras signaling in the visceral mesoderm and that accordingly, Ras signaling is not required in the absence of repression. The key repressor acts downstream of the transcription factor Lameduck and is likely a member of the ETS transcription factor family. Our findings fit with a growing body of data that point to a complex interplay between the Ras pathway, ETS transcription factors, and enhancer binding as a critical mechanism for determining unique responses to Ras signaling.SUMMARYA fundamentally different mechanism is shown for how Ras signaling governs cell fate specification in the Drosophila somatic versus visceral mesoderms, providing insight into how signaling specificity is achieved.

A genetic screen for modifiers of Drosophila decapentaplegic signaling identifies mutations in punt, Mothers against dpp and the BMP-7 homologue, 60A

Development ◽  
1998 ◽  
Vol 125 (9) ◽  
pp. 1759-1768 ◽  
Author(s):  
Y. Chen ◽  
M.J. Riese ◽  
M.A. Killinger ◽  
F.M. Hoffmann
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Genetic Screen ◽  
Biologically Active ◽  
Related Factor ◽  
Type I ◽  
Tgf Beta ◽  
Developmental Processes ◽  
Visceral Mesoderm

decapentaplegic (dpp) is a Transforming Growth Factor beta (TGF-beta)-related growth factor that controls multiple developmental processes in Drosophila. To identify components involved in dpp signaling, we carried out a genetic screen for dominant enhancer mutations of a hypomorphic allele of thick veins (tkv), a type I receptor for dpp. We recovered new alleles of tkv, punt, Mothers against dpp (Mad) and Medea (Med), all of which are known to mediate dpp signaling. We also recovered mutations in the 60A gene which encodes another TGF-beta-related factor in Drosophila. DNA sequence analysis established that all three 60A alleles were nonsense mutations in the prodomain of the 60A polypeptide. These mutations in 60A caused defects in midgut morphogenesis and fat body differentiation. We present evidence that when dpp signaling is compromised, lowering the level of 60A impairs several dpp-dependent developmental processes examined, including the patterning of the visceral mesoderm, the embryonic ectoderm and the imaginal discs. These results provide the first in vivo evidence for the involvement of 60A in the dpp pathway. We propose that 60A activity is required to maintain optimal signaling capacity of the dpp pathway, possibly by forming biologically active heterodimers with Dpp proteins.

serpent, a GATA-like transcription factor gene, induces fat-cell development in Drosophila melanogaster

Development ◽  
2001 ◽  
Vol 128 (7) ◽  
pp. 1193-1200
Author(s):  
S.A. Hayes ◽  
J.M. Miller ◽  
D.K. Hoshizaki
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Body Wall ◽  
Body Wall Muscle ◽  
Ectopic Fat ◽  
Fat Cells ◽  
Transcription Factor Gene ◽  
Fat Cell ◽  
Factor Gene ◽  
Visceral Mesoderm

The GATA-like transcription factor gene serpent is necessary for embryonic fat-cell differentiation in Drosophila (Sam, S., Leise, W. and Hoshizaki, D. K. (1996) Mech. Dev. 60, 197–205) and has been proposed to function in a cell-fate choice between fat cell and somatic gonadal precursors (Moore, L. A., Broihier, H. T., Van Doren, M. and Lehmann, R. (1998) Development 125, 837–44; Riechmann, V., Irion, U., Wilson, R., Grosskortenhaus, R. and Leptin, M. (1997) Development 124, 2915–22). Here, we report that deregulated expression of serpent in the mesoderm induces the formation of ectopic fat cells and prevents the migration and coalescence of the somatic gonadal precursors. The ectopic fat cells do not arise from hyperproliferation of the primary fat-cell clusters but they do associate with the endogenous fat cells to form a fat body that is expanded in both the dorsal/ventral and anterior/posterior axes. Misexpression of serpent also affects the differentiation of muscle cells. Few body-wall muscle precursors are specified and there is a loss of most body-wall muscle fibers. The precursors of the visceral mesoderm are also absent and concomitantly the visceral muscle is absent. We suggest that the ectopic fat cells might originate from cells that have the potential, but do not normally, differentiate into fat cells or from cells that have acquired a fat-cell fate. In light of our results, we discuss the role of serpent in fat-cell specification and in cell fate choices.

scholarly journals osr1 couples intermediate mesoderm cell fate with temporal dynamics of vessel progenitor cell differentiation

2020 ◽  
Author(s):  
Elliot A. Perens ◽  
Jessyka T. Diaz ◽  
Agathe Quesnel ◽  
Amjad Askary ◽  
J. Gage Crump ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Temporal Dynamics ◽  
Bhlh Transcription Factor ◽  
Transcriptional Regulatory Networks ◽  
Mesoderm Cell ◽  
Intermediate Mesoderm ◽  
Transcriptional Regulatory ◽  
Mutant Phenotypes

ABSTRACTTranscriptional regulatory networks refine gene expression boundaries throughout embryonic development to define the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and its neighboring vessel progenitors are poorly understood. Here, we delineate new roles for the zinc finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafish osr1 mutants display decreased IM formation and premature emergence of neighboring lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss of hand2 partially suppresses the osr1 mutant phenotypes. hand2 and osr1 are both expressed in the posterior lateral mesoderm, but osr1 expression decreases dramatically prior to LVP emergence. Overexpressing osr1 inhibits LVP development while enhancing IM formation. Together, our data demonstrate that osr1 modulates both the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels of osr1 and hand2 expression is essential to demarcate the dimensions of kidney and vessel progenitor territories.SUMMARY STATEMENTAnalysis of the osr1 mutant phenotype reveals roles in determining the extent of intermediate mesoderm formation while inhibiting premature differentiation of neighboring vessel progenitors.

scholarly journals NRF2, a Key Regulator of Antioxidants with Two Faces towards Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jaieun Kim ◽  
Young-Sam Keum
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Signal Transduction ◽  
Transcription Factor ◽  
Structure And Function ◽  
Related Factor ◽  
Oxygen Species ◽  
Cellular Functions ◽  
Intracellular Signal ◽  
And Function

While reactive oxygen species (ROS) is generally considered harmful, a relevant amount of ROS is necessary for a number of cellular functions, including the intracellular signal transduction. In order to deal with an excessive amount of ROS, organisms are equipped with a sufficient amount of antioxidants together with NF-E2-related factor-2 (NRF2), a transcription factor that plays a key role in the protection of organisms against environmental or intracellular stresses. While the NRF2 activity has been generally viewed as beneficial to preserve the integrity of organisms, recent studies have demonstrated that cancer cells hijack the NRF2 activity to survive under the oxidative stress and, therefore, a close check must be kept on the NRF2 activity in cancer. In the present review, we briefly highlight important progresses in understanding the molecular mechanism, structure, and function of KEAP1 and NRF2 interaction. In addition, we provide general perspectives that justify conflicting views on the NRF2 activity in cancer.

Sign in / Sign up

Export Citation Format

Share Document