scholarly journals Wild-Type Endoderm Abrogates the Ventral Developmental Defects Associated with GATA-4 Deficiency in the Mouse

1997 ◽  
Vol 189 (2) ◽  
pp. 270-274 ◽  
Author(s):  
Naoko Narita ◽  
Malgorzata Bielinska ◽  
David B. Wilson
Keyword(s):  
Wild Type ◽  
Developmental Defects

scholarly journals The integrin coactivator Kindlin-2 plays a critical role in angiogenesis in mice and zebrafish

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4978-4987 ◽  
Author(s):  
Elzbieta Pluskota ◽  
James J. Dowling ◽  
Natalie Gordon ◽  
Jeffrey A. Golden ◽  
Dorota Szpak ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Critical Role ◽  
Integrin Αvβ3 ◽  
Tube Formation ◽  
Basement Membranes ◽  
Cytoskeletal Protein ◽  
Integrin Expression ◽  
Partial Reduction ◽  
Wild Type ◽  
Developmental Defects

Abstract Kindlin-2, a widely distributed cytoskeletal protein, has been implicated in integrin activation, and its absence is embryonically lethal in mice and causes severe developmental defects in zebrafish. Knockdown of kindlin-2 levels in endothelial cells resulted in defective adhesive and migratory responses, suggesting that angiogenesis might be aberrant even with partial reduction of kindlin-2. This hypothesis has now been tested in the kindlin-2+/− mice. RM1 prostate tumors grown in kindlin-2+/− mice had fewer blood vessels, which were thinner and shorter and supported less tumor growth compared with wild-type littermates. The vessels that did form in the kindlin-2+/− mice lacked smooth muscle cells and pericytes and had thinner basement membranes, indicative of immature vessels. VEGF-induced angiogenesis in matrigel implants was also abnormal in the kindlin-2+/− mice. Vessels in the kindlin-2+/− mice were leaky, and BM transplantation from kindlin-2+/− to WT mice did not correct this defect. Endothelial cells derived from kindlin-2+/− mice had integrin expression levels similar to WT mice but reduced αVβ3-dependent signaling, migration, adhesion, spreading, and tube formation. Developmental angiogenesis was markedly impaired by kindlin-2 morpholinos in zebrafish. Taken together, kindlin-2 plays an important role in pathologic and developmental angiogenesis, which arises from defective activation of integrin αVβ3.

Characterization of the Role of the FluG Protein in Asexual Development of Aspergillus nidulans

Genetics ◽  
2001 ◽  
Vol 158 (3) ◽  
pp. 1027-1036 ◽  
Author(s):  
Cletus A D'Souza ◽  
Bee Na Lee ◽  
Thomas H Adams
Keyword(s):  
Aspergillus Nidulans ◽  
Negative Influence ◽  
Asexual Development ◽  
Wild Type ◽  
Significant Similarity ◽  
Developmental Defects ◽  
Asexual Sporulation ◽  
Type Strains

Abstract We showed previously that a ΔfluG mutation results in a block in Aspergillus nidulans asexual sporulation and that overexpression of fluG activates sporulation in liquid-submerged culture, a condition that does not normally support sporulation of wild-type strains. Here we demonstrate that the entire N-terminal region of FluG (∼400 amino acids) can be deleted without affecting sporulation, indicating that FluG activity resides in the C-terminal half of the protein, which bears significant similarity with GSI-type glutamine synthetases. While FluG has no apparent role in glutamine biosynthesis, we propose that it has an enzymatic role in sporulation factor production. We also describe the isolation of dominant suppressors of ΔfluG(dsg) that should identify components acting downstream of FluG and thereby define the function of FluG in sporulation. The dsgA1 mutation also suppresses the developmental defects resulting from ΔflbA and dominant activating fadA mutations, which both cause constitutive induction of the mycelial proliferation pathway. However, dsgA1 does not suppress the negative influence of these mutations on production of the aflatoxin precursor, sterigmatocystin, indicating that dsgA1 is specific for asexual development. Taken together, our studies define dsgA as a novel component of the asexual sporulation pathway.

Starvation promotes Dictyostelium development by relieving PufA inhibition of PKA translation through the YakA kinase pathway

Development ◽  
1999 ◽  
Vol 126 (14) ◽  
pp. 3263-3274 ◽  
Author(s):  
G.M. Souza ◽  
A.M. da Silva ◽  
A. Kuspa
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Mrna Levels ◽  
Wild Type ◽  
Mobility Shift ◽  
Developmental Defects ◽  
C Protein ◽  
Protein Levels ◽  
Cell Extracts ◽  
Puf Protein

When nutrients are depleted, Dictyostelium cells undergo cell cycle arrest and initiate a developmental program that ensures survival. The YakA protein kinase governs this transition by regulating the cell cycle, repressing growth-phase genes and inducing developmental genes. YakA mutants have a shortened cell cycle and do not initiate development. A suppressor of yakA that reverses most of the developmental defects of yakA- cells, but none of their growth defects was identified. The inactivated gene, pufA, encodes a member of the Puf protein family of translational regulators. Upon starvation, pufA- cells develop precociously and overexpress developmentally important proteins, including the catalytic subunit of cAMP-dependent protein kinase, PKA-C. Gel mobility-shift assays using a 200-base segment of PKA-C's mRNA as a probe reveals a complex with wild-type cell extracts, but not with pufA- cell extracts, suggesting the presence of a potential PufA recognition element in the PKA-C mRNA. PKA-C protein levels are low at the times of development when this complex is detectable, whereas when the complex is undetectable PKA-C levels are high. There is also an inverse relationship between PufA and PKA-C protein levels at all times of development in every mutant tested. Furthermore, expression of the putative PufA recognition elements in wild-type cells causes precocious aggregation and PKA-C overexpression, phenocopying a pufA mutation. Finally, YakA function is required for the decline of PufA protein and mRNA levels in the first 4 hours of development. We propose that PufA is a translational regulator that directly controls PKA-C synthesis and that YakA regulates the initiation of development by inhibiting the expression of PufA. Our work also suggests that Puf protein translational regulation evolved prior to the radiation of metazoan species.

scholarly journals Twinfilin is required for actin-dependent developmental processes in Drosophila

2001 ◽  
Vol 155 (5) ◽  
pp. 787-796 ◽  
Author(s):  
Gudrun Wahlström ◽  
Maria Vartiainen ◽  
Lumi Yamamoto ◽  
Pieta K. Mattila ◽  
Pekka Lappalainen ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Biological Function ◽  
Actin Monomer ◽  
Wild Type ◽  
Developmental Processes ◽  
Developmental Defects ◽  
Actin Bundles ◽  
Morphological Processes ◽  
Encoding Gene ◽  
Different Tissues

The actin cytoskeleton is essential for cellular remodeling and many developmental and morphological processes. Twinfilin is a ubiquitous actin monomer–binding protein whose biological function has remained unclear. We discovered and cloned the Drosophila twinfilin homologue, and show that this protein is ubiquitously expressed in different tissues and developmental stages. A mutation in the twf gene leads to a number of developmental defects, including aberrant bristle morphology. This results from uncontrolled polymerization of actin filaments and misorientation of actin bundles in developing bristles. In wild-type bristles, twinfilin localizes diffusively to cytoplasm and to the ends of actin bundles, and may therefore be involved in localization of actin monomers in cells. We also show that twinfilin and the ADF/cofilin encoding gene twinstar interact genetically in bristle morphogenesis. These results demonstrate that the accurate regulation of size and dynamics of the actin monomer pool by twinfilin is essential for a number of actin-dependent developmental processes in multicellular eukaryotes.

scholarly journals Groucho Oligomerization Is Required for Repression In Vivo

2004 ◽  
Vol 24 (10) ◽  
pp. 4341-4350 ◽  
Author(s):  
Haiyun Song ◽  
Peleg Hasson ◽  
Ze’ev Paroush ◽  
Albert J. Courey
Keyword(s):  
Target Genes ◽  
Cultured Cells ◽  
Coiled Coil ◽  
S2 Cells ◽  
Wild Type ◽  
Developmental Defects ◽  
Conserved Domain ◽  
Wing Disk ◽  
Single Motif

ABSTRACT Drosophila Groucho (Gro) is a member of a family of metazoan corepressors with widespread roles in development. Previous studies indicated that a conserved domain in Gro, termed the Q domain, was required for repression in cultured cells and mediated homotetramerization. Evidence presented here suggests that the Q domain contains two coiled-coil motifs required for oligomerization and repression in vivo. Mutagenesis of the putative hydrophobic faces of these motifs, but not of the hydrophilic faces, prevents the formation of both tetramers and higher order oligomers. Mutagenesis of the hydrophobic faces of both coiled-coil motifs in the context of a Gal4-Gro fusion protein prevents repression of a Gal4-responsive reporter in S2 cells, while mutagenesis of a single motif weakens repression. The finding that the repression directed by the single mutants depends on endogenous wild-type Gro further supports the idea that oligomerization plays a role in repression. Overexpression in the fly of forms of Gro able to oligomerize, but not of a form of Gro unable to oligomerize, results in developmental defects and ectopic repression of Gro target genes in the wing disk. Although the function of several corepressors is suspected to involve oligomerization, these studies represent one of the first direct links between corepressor oligomerization and repression in vivo.

scholarly journals miPEP858/miR858-MYB3-PSK4 module regulates growth and development in Arabidopsis

2021 ◽  
Author(s):  
Poorwa Kamal Badola ◽  
Aashish Sharma ◽  
Himanshi Gautam ◽  
Prabodh Kumar Trivedi
Keyword(s):  
Plant Growth ◽  
Small Molecules ◽  
Growth And Development ◽  
Wild Type ◽  
Developmental Defects ◽  
Over Expression ◽  
Genome Wide ◽  
Exogenous Treatment ◽  
Regulation Of Growth ◽  
Genome Wide Expression

Small molecules, peptides, and miRNAs are the crucial regulators of plant growth. Here, we show the importance of cross-talk between miPEP858a/miR858a and Phytosulfokine (PSK4) in regulating plant growth and development in Arabidopsis. Genome-wide expression analysis suggested modulated expression of PSK4 in miR858 mutant and overexpression, miR858OX, plants. The silencing of PSK4 in miR858OX plants compromised the growth, whereas over-expression of PSK4 in miR858 mutant rescued the developmental defects. The exogenous application of synthetic PSK4 further complemented the plant development in mutant plants. Exogenous treatment of synthetic miPEP858a in PSK4 mutant led to clathrin-mediated internalization of the peptide however did not enhance growth as in the case of wild-type plants. We also demonstrate that the MYB3 is an important molecular component participating in miPEP858a/miR858a-PSK4 module. Finally, our work highlights the signaling between miR858/miPEP858-MYB3-PSK4 in modulating the expression of key elements involved in auxin responses leading to the regulation of growth.

scholarly journals Targeted mutation of the murine goosecoid gene results in craniofacial defects and neonatal death

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2917-2922 ◽  
Author(s):  
G. Yamada ◽  
A. Mansouri ◽  
M. Torres ◽  
E.T. Stuart ◽  
M. Blum ◽  
...  
Keyword(s):  
Body Wall ◽  
Late Phase ◽  
External Auditory Meatus ◽  
Wild Type ◽  
Developmental Defects ◽  
Targeted Mutation ◽  
Craniofacial Defects ◽  
Lower Mandible ◽  
Late Expression

The goosecoid gene encodes a homeodomain-containing protein that has been identified in a number of species and has been implicated in a variety of key developmental processes. Initially suggested to be involved in organizing the embryo during early development, goosecoid has since been demonstrated to be expressed during organogenesis-most notably in the head, the limbs and the ventrolateral body wall. To investigate the role of goosecoid in embryonic development, we have inactivated the gene by gene targeting to generate mice mutant for the goosecoid gene. Mice that are homozygous for the goosecoid mutation do not display a gastrulation phenotype and are born; however, they do not survive more than 24 hours. Analysis of the homozygotes revealed numerous developmental defects affecting those structures in which goosecoid is expressed during its second (late) phase of embryonic expression. Predominantly, these defects involve the lower mandible and its associated musculature including the tongue, the nasal cavity and the nasal pits, as well as the components of the inner ear (malleus, tympanic ring) and the external auditory meatus. Although the observed phenotype is in accordance with the late expression domains of goosecoid in wild-type embryos, we suggest that the lack of an earlier phenotype is the result of functional compensation by other genes.

Cell-type-specific rescue of myosin function during Dictyostelium development defines two distinct cell movements required for culmination

Development ◽  
1998 ◽  
Vol 125 (19) ◽  
pp. 3895-3903 ◽  
Author(s):  
T.L. Chen ◽  
W.A. Wolf ◽  
R.L. Chisholm
Keyword(s):  
Fluorescent Protein ◽  
Video Recording ◽  
Time Lapse ◽  
Active Movement ◽  
Upward Movement ◽  
Wild Type ◽  
Cell Type ◽  
Developmental Defects ◽  
Distinct Cell ◽  
Cell Type Specific

Mutant Dictyostelium cells lacking any of the component polypeptides of myosin II exhibit developmental defects. To define myosin's role in establishing Dictyostelium's developmental pattern, we have rescued myosin function in a myosin regulatory light chain null mutant (mlcR-) using cell-type-specific promoters. While mlcR- cells fail to progress beyond the mound stage, expression of RLC from the prestalk promoter, ecmA, produces culminants with normal stalks but with defects in spore cell localization. When GFP-marked prestalk and prespore cells expressing ecmA-RLC are mixed with wild-type cells, the mislocalization of prestalk cells, but not prespore cells, is rescued. Time-lapse video recording of ecmA-RLC cells showed that the posterior prespore zone failed to undergo a contraction important for the upward movement of prespore cells. Prespore cells marked with green fluorescent protein (GFP) failed to move toward the tip with the spiral motion typical of wild type. In contrast, expression of RLC in prespore cells using the psA promoter produced balloon-like structures reminiscent of sorocarps but lacking stalks. GFP-labeled prespore cells showed a spiral movement toward the top of the structures. Expression of RLC from the psA promoter restores the normal localization of psA-GFP cells, but not ecmA-GFP cells. These results define two distinct, myosin-dependent movements that are required for establishing a Dictyostelium fruiting body: stalk extension and active movement of the prespore zone that ensures proper placement of the spores atop the stalk. The approach used in these studies provides a direct means of testing the role of cell motility in distinct cell types during a morphogenetic program.

scholarly journals Auxin binding protein 1 (ABP1) is not required for either auxin signaling or Arabidopsis development

2015 ◽  
Vol 112 (7) ◽  
pp. 2275-2280 ◽  
Author(s):  
Yangbin Gao ◽  
Yi Zhang ◽  
Da Zhang ◽  
Xinhua Dai ◽  
Mark Estelle ◽  
...  
Keyword(s):  
Binding Protein ◽  
Start Codon ◽  
Null Alleles ◽  
Auxin Signaling ◽  
Wild Type ◽  
Auxin Receptor ◽  
Developmental Defects ◽  
Auxin Binding ◽  
Dna Insertion ◽  
Auxin Binding Protein

Auxin binding protein 1 (ABP1) has been studied for decades. It has been suggested that ABP1 functions as an auxin receptor and has an essential role in many developmental processes. Here we present our unexpected findings that ABP1 is neither required for auxin signaling nor necessary for plant development under normal growth conditions. We used our ribozyme-based CRISPR technology to generate an Arabidopsis abp1 mutant that contains a 5-bp deletion in the first exon of ABP1, which resulted in a frameshift and introduction of early stop codons. We also identified a T-DNA insertion abp1 allele that harbors a T-DNA insertion located 27 bp downstream of the ATG start codon in the first exon. We show that the two new abp1 mutants are null alleles. Surprisingly, our new abp1 mutant plants do not display any obvious developmental defects. In fact, the mutant plants are indistinguishable from wild-type plants at every developmental stage analyzed. Furthermore, the abp1 plants are not resistant to exogenous auxin. At the molecular level, we find that the induction of known auxin-regulated genes is similar in both wild-type and abp1 plants in response to auxin treatments. We conclude that ABP1 is not a key component in auxin signaling or Arabidopsis development.

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