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- Mörck, Catarina, 1972, et al.
(författare)
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A genetic analysis of axon guidance in the C elegans pharynx
- 2003
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Ingår i: Developmental Biology. - 1095-564X .- 0012-1606. ; 260:1, s. 158-175
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Tidskriftsartikel (refereegranskat)abstract
- We wish to understand how the trajectories of the twenty pharyngeal neurons of C. elegans are established. In this study we focused on the two bilateral M2 pharyngeal motorneurons, which each have their cell body located in the posterior bulb and send one axon through the isthmus and into the metacorpus. We used a GFP reporter to visualize these neurons in cell-autonomous and cell-non-autonomous axon guidance mutant backgrounds, as well as other mutant classes. Our main findings are: 1) Mutants with impaired growth cone functions, such as unc-6, unc-51, unc-73 and sax-3, often exhibit abnormal terminations and inappropriate trajectories at the distal ends of the M2 axons, i.e. within the metacorpus; and 2) Growth cone function mutants never exhibit abnormalities in the proximal part of the M2 neuron trajectories, i.e. between the cell body and the metacorpus. Our results suggest that the proximal and distal trajectories are established using distinct mechanisms, including a growth cone-independent process to establish the proximal trajectory. We isolated five novel mutants in a screen for worms exhibiting abnormal morphology of the M2 neurons. These mutants define a new gene class designated mnm (M neuron morphology abnormal). © 2003 Elsevier Science (USA). All rights reserved.
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| 2. |
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| 3. |
- Abramsson, Alexandra, 1973, et al.
(författare)
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The zebrafish amyloid precursor protein-b is required for motor neuron guidance and synapse formation.
- 2013
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Ingår i: Developmental biology. - : Elsevier BV. - 1095-564X .- 0012-1606. ; 381:2, s. 377-88
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Tidskriftsartikel (refereegranskat)abstract
- The amyloid precursor protein (APP) is a transmembrane protein mostly recognized for its association with Alzheimer's disease. The physiological function of APP is still not completely understood much because of the redundancy between genes in the APP family. In this study we have used zebrafish to study the physiological function of the zebrafish APP homologue, appb, during development. We show that appb is expressed in post-mitotic neurons in the spinal cord. Knockdown of appb by 50-60% results in a behavioral phenotype with increased spontaneous coiling and prolonged touch-induced activity. The spinal cord motor neurons in these embryos show defective formation and axonal outgrowth patterning. Reduction in Appb also results in patterning defects and changed density of pre- and post-synapses in the neuromuscular junctions. Together, our data show that development of functional locomotion in zebrafish depends on a critical role of Appb in the patterning of motor neurons and neuromuscular junctions.
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| 4. |
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| 5. |
- Ali, Zaheer, et al.
(författare)
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Synchronized tissue-scale vasculogenesis and ubiquitous lateral sprouting underlie the unique architecture of the choriocapillaris
- 2020
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Ingår i: Developmental Biology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0012-1606 .- 1095-564X. ; 457:2, s. 206-214
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Tidskriftsartikel (refereegranskat)abstract
- The choriocapillaris is an exceptionally high density, two-dimensional, sheet-like capillary network, characterized by the highest exchange rate of nutrients for waste products per area in the organism. These unique morphological and physiological features are critical for supporting the extreme metabolic requirements of the outer retina needed for vision. The developmental mechanisms and processes responsible for generating this unique vascular network remain, however, poorly understood. Here we take advantage of the zebrafish as a model organism for gaining novel insights into the cellular dynamics and molecular signaling mechanisms involved in the development of the choriocapillaris. We show for the first time that zebrafish have a choriocapillaris highly similar to that in mammals, and that it is initially formed by a novel process of synchronized vasculogenesis occurring simultaneously across the entire outer retina. This initial vascular network expands by un-inhibited sprouting angiogenesis whereby all endothelial cells adopt tip-cell characteristics, a process which is sustained throughout embryonic and early post-natal development, even after the choriocapillaris becomes perfused. Ubiquitous sprouting was maintained by continuous VEGF-VEGFR2 signaling in endothelial cells delaying maturation until immediately before stages where vision becomes important for survival, leading to the unparalleled high density and lobular structure of this vasculature. Sprouting was throughout development limited to two dimensions by Bruchs membrane and the sclera at the anterior and posterior surfaces respectively. These novel cellular and molecular mechanisms underlying choriocapillaris development were recapitulated in mice. In conclusion, our findings reveal novel mechanisms underlying the development of the choriocapillaris during zebrafish and mouse development. These results may explain the uniquely high density and sheet-like organization of this vasculature.
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| 6. |
- Amienl, Aldine R., et al.
(författare)
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A bipolar role of the transcription factor ERG for cnidarian germ layer formation and apical domain patterning
- 2017
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Ingår i: Developmental Biology. - : Elsevier BV. - 0012-1606 .- 1095-564X. ; 430:2, s. 346-361
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Tidskriftsartikel (refereegranskat)abstract
- Germ layer formation and axial patterning are biological processes that are tightly linked during embryonic development of most metazoans. In addition to canonical WNT, it has been proposed that ERK-MAPK signaling is involved in specifying oral as well as aboral territories in cnidarians. However, the effector and the molecular mechanism underlying latter phenomenon is unknown. By screening for potential effectors of ERK-MAPK signaling in both domains, we identified a member of the ETS family of transcription factors, Nverg that is bipolarily expressed prior to gastrulation. We further describe the crucial role of NvERG for gastrulation, endomesoderm as well as apical domain formation. The molecular characterization of the obtained NvERG knock-down phenotype using previously described as well as novel potential downstream targets, provides evidence that a single transcription factor, NvERG, simultaneously controls expression of two different sets of downstream targets, leading to two different embryonic gene regulatory networks (GRNs) in opposite poles of the developing embryo. We also highlight the molecular interaction of cWNT and MEK/ERK/ERG signaling that provides novel insight into the embryonic axial organization of Nematostella, and show a cWNT repressive role of MEK/ERK/ERG signaling in segregating the endomesoderm in two sub-domains, while a common input of both pathways is required for proper apical domain formation. Taking together, we build the first blueprint for a global cnidarian embryonic GRN that is the foundation for additional gene specific studies addressing the evolution of embryonic and larval development.
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| 8. |
- Ando, Koji, et al.
(författare)
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Conserved and context-dependent roles for pdgfrb signaling during zebrafish vascular mural cell development
- 2021
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Ingår i: Developmental Biology. - : Elsevier. - 0012-1606 .- 1095-564X. ; 479, s. 11-22
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Tidskriftsartikel (refereegranskat)abstract
- Platelet derived growth factor beta and its receptor, Pdgfrb, play essential roles in the development of vascular mural cells, including pericytes and vascular smooth muscle cells. To determine if this role was conserved in zebrafish, we analyzed pdgfb and pdgfrb mutant lines. Similar to mouse, pdgfb and pdgfrb mutant zebrafish lack brain pericytes and exhibit anatomically selective loss of vascular smooth muscle coverage. Despite these defects, pdgfrb mutant zebrafish did not otherwise exhibit circulatory defects at larval stages. However, beginning at juvenile stages, we observed severe cranial hemorrhage and vessel dilation associated with loss of pericytes and vascular smooth muscle cells in pdgfrb mutants. Similar to mouse, pdgfrb mutant zebrafish also displayed structural defects in the glomerulus, but normal development of hepatic stellate cells. We also noted defective mural cell investment on coronary vessels with concomitant defects in their development. Together, our studies support a conserved requirement for Pdgfrb signaling in mural cells. In addition, these zebrafish mutants provide an important model for definitive investigation of mural cells during early embryonic stages without confounding secondary effects from circulatory defects.
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| 9. |
- Anguita, Eduardo, et al.
(författare)
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A somatic mutation of GFI1B identified in leukemia alters cell fate via a SPI1 (PU.1) centered genetic regulatory network.
- 2016
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Ingår i: Developmental Biology. - : Elsevier BV. - 1095-564X .- 0012-1606. ; 411:2, s. 277-286
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Tidskriftsartikel (refereegranskat)abstract
- We identify a mutation (D262N) in the erythroid-affiliated transcriptional repressor GFI1B, in an acute myeloid leukemia (AML) patient with antecedent myelodysplastic syndrome (MDS). The GFI1B-D262N mutant functionally antagonizes the transcriptional activity of wild-type GFI1B. GFI1B-D262N promoted myelomonocytic versus erythroid output from primary human hematopoietic precursors and enhanced cell survival of both normal and MDS derived precursors. Re-analysis of AML transcriptome data identifies a distinct group of patients in whom expression of wild-type GFI1B and SPI1 (PU.1) have an inverse pattern. In delineating this GFI1B-SPI1 relationship we show that (i) SPI1 is a direct target of GFI1B, (ii) expression of GFI1B-D262N produces elevated expression of SPI1, and (iii) SPI1-knockdown restores balanced lineage output from GFI1B-D262N-expressing precursors. These results table the SPI1-GFI1B transcriptional network as an important regulatory axis in AML as well as in the development of erythroid versus myelomonocytic cell fate.
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| 10. |
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