Cost-precision trade-off relation determines the optimal morphogen gradient for accurate biological pattern formation

Mapping Intimacies ◽

10.1101/2021.04.14.439772 ◽

2021 ◽

Author(s):

Yonghyun Song ◽

Changbong Hyeon

Keyword(s):

Target Gene ◽

Characteristic Length ◽

Fruit Fly ◽

Local Source ◽

Imaginal Disk ◽

Degradation Model ◽

Animal Development ◽

Large Gradient ◽

Boundary Position ◽

Biological Pattern Formation

Spatial boundaries growing into macroscopic structures through animal development originate from the pre-patterning of tissues by signaling molecules, called morphogens. To establish accurate boundaries, the morphogen concentration which thresholds the expression of target gene at the boundary should be precise enough, exhibiting large gradient and small fluctuations. Producing more morphogens would better serve to shape more precise target boundaries; however, it incurs more thermodynamic cost. In the classical diffusion-degradation model of morphogen profile formation, the morphogens synthesized from a local source display an exponentially decaying concentration profile with a characteristic length λ. Our theory suggests that in order to attain a precise morphogen profile with the minimal cost, λ should be roughly half the distance to the target boundary position from the source, so that the boundary is formed at the position where the morphogen concentration is ~10% of the value at the source. Remarkably, we find that the well characterized morphogens that pattern the fruit fly embryo and wing imaginal disk form profiles with nearly optimal λ, which underscores the thermodynamic cost as a key physical constraint in the morphogen profile formation.

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Cost-precision trade-off relation determines the optimal morphogen gradient for accurate biological pattern formation

eLife ◽

10.7554/elife.70034 ◽

2021 ◽

Vol 10 ◽

Author(s):

Yonghyun Song ◽

Changbong Hyeon

Keyword(s):

Target Gene ◽

Characteristic Length ◽

Morphogen Gradient ◽

Local Source ◽

Minimal Cost ◽

Imaginal Disk ◽

Animal Development ◽

Boundary Position ◽

Biological Pattern Formation ◽

Boundary Location

Spatial boundaries formed during animal development originate from the pre-patterning of tissues by signaling molecules, called morphogens. The accuracy of boundary location is limited by the fluctuations of morphogen concentration that thresholds the expression level of target gene. Producing more morphogen molecules, which gives rise to smaller relative fluctuations, would better serve to shape more precise target boundaries; however, it incurs more thermodynamic cost. In the classical diffusion-depletion model of morphogen profile formation, the morphogen molecules synthesized from a local source display an exponentially decaying concentration profile with a characteristic length λ. Our theory suggests that in order to attain a precise profile with the minimal cost, λ should be roughly half the distance to the target boundary position from the source. Remarkably, we find that the profiles of morphogens that pattern the Drosophila embryo and wing imaginal disk are formed with nearly optimal λ. Our finding underscores the thermodynamic cost as a key physical constraint in the morphogen profile formation in Drosophila development.

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The microtubule motor cytoplasmic dynein is required for spindle orientation during germline cell divisions and oocyte differentiation in Drosophila

Development ◽

10.1242/dev.124.12.2409 ◽

1997 ◽

Vol 124 (12) ◽

pp. 2409-2419 ◽

Cited By ~ 15

Author(s):

M. McGrail ◽

T.S. Hays

Keyword(s):

Asymmetric Cell Division ◽

Fruit Fly ◽

Cytoplasmic Dynein ◽

Spindle Orientation ◽

Chain Gene ◽

Animal Development ◽

Dynein Motor ◽

Microtubule Motor ◽

Two Stages ◽

Oocyte Differentiation

During animal development cellular differentiation is often preceded by an asymmetric cell division whose polarity is determined by the orientation of the mitotic spindle. In the fruit fly, Drosophila melanogaster, the oocyte differentiates in a 16-cell syncytium that arises from a cystoblast which undergoes 4 synchronous divisions with incomplete cytokinesis. During these divisions, spindle orientation is highly ordered and is thought to impart a polarity to the cyst that is necessary for the subsequent differentiation of the oocyte. Using mutations in the Drosophila cytoplasmic dynein heavy chain gene, Dhc64C, we show that cytoplasmic dynein is required at two stages of oogenesis. Early in oogenesis, dynein mutations disrupt spindle orientation in dividing cysts and block oocyte determination. The localization of dynein in mitotic cysts suggests spindle orientation is mediated by the microtubule motor cytoplasmic dynein. Later in oogenesis, dynein function is necessary for proper differentiation, but does not appear to participate in morphogen localization within the oocyte. These results provide evidence for a novel developmental role for the cytoplasmic dynein motor in cellular determination and differentiation.

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Understanding the role of lipids and lipoproteins in development

Development ◽

10.1242/dev.186411 ◽

2020 ◽

Vol 147 (24) ◽

pp. dev186411 ◽

Cited By ~ 3

Author(s):

Wilhelm Palm ◽

Jonathan Rodenfels

Keyword(s):

Fruit Fly ◽

Membrane Lipid ◽

Lipid Homeostasis ◽

Hedgehog Signalling ◽

Animal Development ◽

Lipid Species ◽

Hedgehog Signalling Pathway ◽

Living Organisms ◽

Lipids And Lipoproteins

ABSTRACTLipids exert diverse functions in living organisms. They form cellular membranes, store and transport energy and play signalling roles. Some lipid species function in all of these processes, making them ideal candidates to coordinate metabolism with cellular homeostasis and animal development. This theme was central to Suzanne Eaton's research in the fruit fly, Drosophila. Here, we discuss her work on membrane lipid homeostasis in changing environments and on functions for lipids in the Hedgehog signalling pathway. We further highlight lipoproteins as inter-organ carriers of lipids and lipid-linked morphogens, which communicate dietary and developmental signals throughout the organism.

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Walter Jakob Gehring. 20 March 1939—29 May 2014

Biographical Memoirs of Fellows of the Royal Society ◽

10.1098/rsbm.2021.0011 ◽

2021 ◽

Author(s):

Ginés Morata ForMemRS ◽

Markus Affolter

Keyword(s):

Molecular Mechanisms ◽

Gifted Students ◽

Fruit Fly ◽

Football Player ◽

Molecular Techniques ◽

General Interest ◽

Animal Development ◽

Developmental Problems ◽

Scientific Disciplines ◽

Great Energy

Walter Jakob Gehring was one of the most influential developmental biologists of the last 50 years. First as a student with Professor Ernst Hadorn in Zurich, later as a postdoc in Yale and finally as group leader in Basel, he was involved in a number of major discoveries that had a profound impact in the understanding of the genetic and molecular mechanisms of animal development, not only for the fruit fly Drosophila but for the whole animal kingdom. Throughout his career Gehring demonstrated an outstanding ability to recognize key problems and then to push experimental work on these problems with great energy. Gehring pioneered the application of molecular techniques to developmental problems, an approach that was at the root of many of his contributions. His laboratory was involved in a number of key findings: the first cloning of a Hox gene, the discovery of the homeobox, the enhancer trap method, and the remarkable conservation of features of the visual system in metazoans. He was an excellent speaker, with special ability to emphasize the relevant aspects of his work and to draw conclusions of general interest. This attracted a number of gifted students and postdocs who were key for the success of his research group. Passionately interested in science, he was also very excited about other scientific disciplines; he was an accomplished bird watcher and was also fascinated by marine life. But he also had non-scientific interests, too; he claimed to be an excellent football player and frequently commented that he had had to decide whether to be a scientist or a professional footballer. He decided on the former, but one wonders if he might have been a Swiss version of Messi or Ronaldo.

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dTcf/Pangolinsuppresses growth and tumor formation inDrosophila

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1816981116 ◽

2019 ◽

Vol 116 (28) ◽

pp. 14055-14064 ◽

Cited By ~ 1

Author(s):

Shilin Song ◽

Diana Andrejeva ◽

Flávia C. P. Freitas ◽

Stephen M. Cohen ◽

Héctor Herranz

Keyword(s):

Transcription Factor ◽

Target Genes ◽

Normal Development ◽

Tumor Development ◽

Growth Control ◽

Tissue Growth ◽

Tumor Formation ◽

Imaginal Disk ◽

Animal Development ◽

Transcription Factor 1

Wnt/Wingless (Wg) signaling controls many aspects of animal development and is deregulated in different human cancers. The transcription factor dTcf/Pangolin (Pan) is the final effector of the Wg pathway inDrosophilaand has a dual role in regulating the expression of Wg target genes. In the presence of Wg, dTcf/Pan interacts with β-catenin/Armadillo (Arm) and induces the transcription of Wg targets. In absence of Wg, dTcf/Pan partners with the transcriptional corepressor TLE/Groucho (Gro) and inhibits gene expression. Here, we use the wing imaginal disk ofDrosophilaas a model to examine the functions that dTcf/Pan plays in a proliferating epithelium. We report a function of dTcf/Pan in growth control and tumorigenesis. Our results show that dTcf/Pan can limit tissue growth in normal development and suppresses tumorigenesis in the context of oncogene up-regulation. We identify the conserved transcription factorsSox box protein 15(Sox15) andFtz transcription factor 1(Ftz-f1) as genes controlled by dTcf/Pan involved in tumor development. In conclusion, this study reports a role for dTcf/Pan as a repressor of normal and oncogenic growth and identifies the genes inducing tumorigenesis downstream of dTcf/Pan.

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The Phenotypic Effect of Cardamom oil on the Developmental Stages of Drosophila Melanogaster

International Journal of Scientific Research in Science and Technology ◽

10.32628/ijsrst218534 ◽

2021 ◽

pp. 225-231

Author(s):

Dr. Y. D. Akhare ◽

H. A. Patharikar

Keyword(s):

Drosophila Melanogaster ◽

Developmental Stages ◽

Culture Media ◽

Model Organism ◽

Fruit Fly ◽

Life Stages ◽

Human Genetic Disease ◽

Phenotypic Effect ◽

Animal Development ◽

Food And Drink

The fruit fly Drosophila melanogaster has been extensively studied as a model organism for genetic investigation. It also has many characteristics which make it an ideal organism for the study of animal development and behaviour, neurobiology and human genetic disease and condition. Drosophila melanogaster share several basic biological and chemical neurological and physiological similarities with mammals. In the present study, we noted the phenotypic effect of cardamom oil on the different stages of Drosophila melanogaster. The fruit flies were grown on 10-gram culture media supplemented with different concentration of cardamom oil (0.5µl, 1 µl, 2.5 µl). Further, the size and growth of different life stages of Drosophila melanogaster were observed and total protein estimated from it.The increase in the size and protein concentration in different life stages of controlled Drosophila melanogaster were recorded. Cardamom is a highly valued herbal spice used in tropical and subtropical Asia. cardamom is used as a flavouring and cooking spices in both food and drink and as a medicine.

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Positive autoregulation of lag-1 in response to LIN-12 activation in cell fate decisions during C. elegans reproductive system development

Development ◽

10.1242/dev.193482 ◽

2020 ◽

Vol 147 (18) ◽

pp. dev193482

Author(s):

Katherine Leisan Luo ◽

Ryan S. Underwood ◽

Iva Greenwald

Keyword(s):

Cell Fate ◽

Reproductive System ◽

Target Gene ◽

System Development ◽

Animal Development ◽

Cell Fate Decisions ◽

C Elegans ◽

Spatiotemporal Regulation ◽

Target Gene Transcription ◽

Notch Activation

ABSTRACTDuring animal development, ligand binding releases the intracellular domain of LIN-12/Notch by proteolytic cleavage to translocate to the nucleus, where it associates with the DNA-binding protein LAG-1/CSL to activate target gene transcription. We investigated the spatiotemporal regulation of LAG-1/CSL expression in Caenorhabditis elegans and observed that an increase in endogenous LAG-1 levels correlates with LIN-12/Notch activation in different cell contexts during reproductive system development. We show that this increase is via transcriptional upregulation by creating a synthetic endogenous operon, and identified an enhancer region that contains multiple LAG-1 binding sites (LBSs) embedded in a more extensively conserved high occupancy target (HOT) region. We show that these LBSs are necessary for upregulation in response to LIN-12/Notch activity, indicating that lag-1 engages in direct positive autoregulation. Deletion of the HOT region from endogenous lag-1 reduced LAG-1 levels and abrogated positive autoregulation, but did not cause hallmark cell fate transformations associated with loss of lin-12/Notch or lag-1 activity. Instead, later somatic reproductive system defects suggest that proper transcriptional regulation of lag-1 confers robustness to somatic reproductive system development.

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Reaction diffusion modelling of biological pattern formation: Application to the embryogenesis of Drosophila melanogaster

Canadian Journal of Physics ◽

10.1139/p90-112 ◽

1990 ◽

Vol 68 (9) ◽

pp. 772-777 ◽

Cited By ~ 6

Author(s):

M. J. Lyons ◽

L. G. Harrison ◽

B. C. Lakowski ◽

T. C. Lacalli

Keyword(s):

Drosophila Melanogaster ◽

Pattern Formation ◽

Diffusion Theory ◽

Reaction Diffusion ◽

Fruit Fly ◽

General Plan ◽

Early Results ◽

Segmentation Pattern ◽

Biological Pattern Formation ◽

Biological Development

The general problem of pattern formation in biological development is described. One possible type of general solution, reaction–diffusion theory, is outlined, together with the difficulties involved in definite experimental confirmation or rejection of it. A specific biological problem, the origin of the segmentation pattern in the fruit fly Drosophila melanogaster, is discussed. The general plan of our program of computational work to study how this could arise by reaction–diffusion is indicated, with some early results.

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Alleviation of pain and depression by specific neural transplants: Fine structural correlates

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100129966 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1066-1067

Author(s):

George D. Pappas ◽

Jacqueline Sagen

Keyword(s):

Opioid Peptides ◽

Chromaffin Cells ◽

Pain Sensitivity ◽

Opioid Peptide ◽

Local Source ◽

Pain Models ◽

Neural Transplants ◽

Adrenergic Antagonists ◽

Csf Levels ◽

Donor Source

We have been interested in the use of neural transplants mainly as a local source of neuroactive substances, rather than as a replacement for damaged neural circuities. In particular, we have been exploring the possibilities of reducing pain by transplants of opioid peptide producing cells, and reducing depression by transplants of monoamine-producing cells. For the past several years, work in our laboratory has demonstrated in both acute and chronic pain models that transplantation of adrenal medullary tissue or isolated chromaffin cells into CNS pain modulatory regions can reduce pain sensitivity in rodents. Chromaffin cells were chosen as donor source since they produce high levels of both opioid peptides and catecholamines, substances which independently, and probably synergistically, reduce pain sensitivity when injected locally into the spinal cord. The analgesia produced by these transplants most likely results from the release of both opioid peptides and catecholamines, since it can be blocked or attenuated by opiate or adrenergic antagonists, respectively. Furthermore, CSF levels of met-enkephalin and catecholamines are increased by the transplants.

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