Feedback control of morphogen gradient scale

SUMMARYGradients of the morphogen decapentaplegic (Dpp) pattern Drosophila wing imaginal discs, establishing gene expression boundaries at specific locations. As discs grow, Dpp gradients expand, keeping relative boundary positions approximately stationary. Such scaling fails in mutants for Pentagone (pent), a gene repressed by Dpp that encodes a diffusible protein that expands Dpp gradients. Although these properties fit a recent mathematical model of automatic gradient scaling, we show here that Pent lacks a property essential to that model—the ability to spread with minimal loss throughout the morphogen field. Instead, Pent’s actions appear confined to within a few cell diameters of its site of synthesis, and can be phenocopied by manipulating non-diffusible targets of Pent strictly within the Pent expression domain. Through genetic manipulation and mathematical modeling we develop an alternative model of scaling, driven by feedback down-regulation of Dpp receptors and co-receptors. Among the model’s predictions is a size limit beyond which scaling fails—something we observe directly in wing discs.

Download Full-text

The knirps and knirps-related genes organize development of the second wing vein in Drosophila

Development ◽

10.1242/dev.125.21.4145 ◽

1998 ◽

Vol 125 (21) ◽

pp. 4145-4154 ◽

Cited By ~ 11

Author(s):

K. Lunde ◽

B. Biehs ◽

U. Nauber ◽

E. Bier

Keyword(s):

Target Gene ◽

Positional Information ◽

Transcription Unit ◽

Expression Domain ◽

Anterior Border ◽

Wing Vein ◽

Cis Acting ◽

Gap Gene ◽

Wing Imaginal Discs ◽

Wing Discs

The neighboring homologous knirps (kni) and knirps-related (knrl) genes in Drosophila encode transcription factors in the steroid hormone receptor superfamily. During early embryogenesis, kni functions as a gap gene to control expression of segmentation genes within the abdominal region of the embryo. In this study, we present evidence that kni and knrl link A/P positional information in larval wing imaginal discs to morphogenesis of the second longitudinal wing vein (L2). We show that kni and knrl are expressed in similar narrow stripes corresponding to the position of the L2 primordium. The kni and knrl L2 stripes abut the anterior border of the broad central expression domain of the Dpp target gene spalt major (salm). We provide evidence that radius incompletus (ri), a well-known viable mutant lacking the L2 vein, is a regulatory mutant of the kni/knrl locus. In ri mutant wing discs, kni and knrl fail to be expressed in the L2 primordium. In addition, the positions of molecular breakpoints in the kni/knrl locus indicate that the ri function is provided by cis-acting sequences upstream of the kni transcription unit. Epistasis tests reveal that the kni/knrl locus functions downstream of spalt major (salm) and upstream of genes required to initiate vein-versus-intervein differentiation. Mis-expression experiments suggest that kni and knrl expressing cells inhibit neighboring cells from becoming vein cells. Finally, kni and knrl are likely to refine the L2 position by positively auto-regulating their own expression and by providing negative feedback to repress salm expression. We propose a model in which the combined activities of kni and knrl organize development of the L2 vein in the appropriate position.

Download Full-text

Gene expression following induction of regeneration in Drosophila wing imaginal discs. Expression profile of regenerating wing discs

BMC Developmental Biology ◽

10.1186/1471-213x-10-94 ◽

2010 ◽

Vol 10 (1) ◽

pp. 94 ◽

Cited By ~ 36

Author(s):

Enrique Blanco ◽

Marina Ruiz-Romero ◽

Sergi Beltran ◽

Manel Bosch ◽

Adrià Punset ◽

...

Keyword(s):

Gene Expression ◽

Expression Profile ◽

Imaginal Discs ◽

Drosophila Wing ◽

Wing Imaginal Discs ◽

Wing Discs

Download Full-text

Testicular Function: From Gene Expression to Genetic Manipulation

10.1007/978-3-662-03671-6 ◽

1998 ◽

Keyword(s):

Gene Expression ◽

Genetic Manipulation ◽

Testicular Function

Download Full-text

Environmental RNAi pathways in the two-spotted spider mite

BMC Genomics ◽

10.1186/s12864-020-07322-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Mosharrof Mondal ◽

Jacob Peter ◽

Obrie Scarbrough ◽

Alex Flynt

Keyword(s):

Gene Expression ◽

Small Rna ◽

Spider Mite ◽

Genetic Manipulation ◽

Model Organisms ◽

Rnai Pathway ◽

Plant Host ◽

Rnai Technology ◽

Two Spotted Spider Mite ◽

Multicellular Organisms

Abstract Background RNA interference (RNAi) regulates gene expression in most multicellular organisms through binding of small RNA effectors to target transcripts. Exploiting this process is a popular strategy for genetic manipulation and has applications that includes arthropod pest control. RNAi technologies are dependent on delivery method with the most convenient likely being feeding, which is effective in some animals while others are insensitive. The two-spotted spider mite, Tetranychus urticae, is prime candidate for developing RNAi approaches due to frequent occurrence of conventional pesticide resistance. Using a sequencing-based approach, the fate of ingested RNAs was explored to identify features and conditions that affect small RNA biogenesis from external sources to better inform RNAi design. Results Biochemical and sequencing approaches in conjunction with extensive computational assessment were used to evaluate metabolism of ingested RNAs in T. urticae. This chelicerae arthropod shows only modest response to oral RNAi and has biogenesis pathways distinct from model organisms. Processing of synthetic and plant host RNAs ingested during feeding were evaluated to identify active substrates for spider mite RNAi pathways. Through cataloging characteristics of biochemically purified RNA from these sources, trans-acting small RNAs could be distinguished from degradation fragments and their origins documented. Conclusions Using a strategy that delineates small RNA processing, we found many transcripts have the potential to enter spider mite RNAi pathways, however, trans-acting RNAs appear very unstable and rare. This suggests potential RNAi pathway substrates from ingested materials are mostly degraded and infrequently converted into regulators of gene expression. Spider mites infest a variety of plants, and it would be maladaptive to generate diverse gene regulators from dietary RNAs. This study provides a framework for assessing RNAi technology in organisms where genetic and biochemical tools are absent and benefit rationale design of RNAi triggers for T.urticae.

Download Full-text

Genetic manipulation of RPS5 gene expression modulates the initiation of commitment of MEL cells to erythroid maturation: Implications in understanding ribosomopathies

International Journal of Oncology ◽

10.3892/ijo.2015.3017 ◽

2015 ◽

Vol 47 (1) ◽

pp. 303-314 ◽

Cited By ~ 3

Author(s):

IOANNIS S. VIZIRIANAKIS ◽

ELENI T. PAPACHRISTOU ◽

PANAGIOTIS ANDREADIS ◽

ELENA ZOPOUNIDOU ◽

CHRISTINA N. MATRAGKOU ◽

...

Keyword(s):

Gene Expression ◽

Genetic Manipulation ◽

Erythroid Maturation

Download Full-text

Expression of the atrial-specific myosin heavy chain AMHC1 and the establishment of anteroposterior polarity in the developing chicken heart

Development ◽

10.1242/dev.120.4.871 ◽

1994 ◽

Vol 120 (4) ◽

pp. 871-883 ◽

Cited By ~ 14

Author(s):

K.E. Yutzey ◽

J.T. Rhee ◽

D. Bader

Keyword(s):

Gene Expression ◽

Retinoic Acid ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Cardiac Myocyte ◽

Anterior Segment ◽

Heart Cells ◽

Heart Tube ◽

Expression Domain ◽

Chicken Heart

A unique myosin heavy chain cDNA (AMHC1), which is expressed exclusively in the atria of the developing chicken heart, was isolated and used to study the generation of diversified cardiac myocyte cell lineages. The pattern of AMHC1 gene expression during heart formation was determined by whole-mount in situ hybridization. AMHC1 is first activated in the posterior segment of the heart when these myocytes initially differentiate (Hamburger and Hamilton stage 9+). The anterior segment of the heart at this stage does not express AMHC1 although the ventricular myosin heavy chain isoform is strongly expressed beginning at stage 8+. Throughout chicken development, AMHC1 continues to be expressed in the posterior heart tube as it develops into the diversified atria. The early activation of AMHC1 expression in the posterior cardiac myocytes suggests that the heart cells are diversified when they differentiate initially and that the anterior heart progenitors differ from the posterior heart progenitors in their myosin isoform gene expression. The expression domain of AMHC1 can be expanded anteriorly within the heart tube by treating embryos with retinoic acid as the heart primordia fuse. Embryos treated with retinoic acid prior to the initiation of fusion of the heart primordia express AMHC1 throughout the entire heart-forming region and fusion of the heart primordia is inhibited. These data indicate that retinoic acid treatment produces an expansion of the posterior (atrial) domain of the heart and suggests that diversified fates of cardiomyogenic progenitors can be altered.

Download Full-text

Minireview: Transcriptional Regulation in Development of Bone

Endocrinology ◽

10.1210/en.2004-1343 ◽

2005 ◽

Vol 146 (3) ◽

pp. 1012-1017 ◽

Cited By ~ 108

Author(s):

Tatsuya Kobayashi ◽

Henry Kronenberg

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Transcription Factors ◽

Bone Cells ◽

Genetic Manipulation ◽

Bone Development ◽

Regulation Of Gene Expression ◽

Bone Cell ◽

Cellular Functions ◽

Multiple Differentiation

Regulation of gene expression by transcription factors is one of the major mechanisms for controlling cellular functions. Recent advances in genetic manipulation of model animals has allowed the study of the roles of various genes and their products in physiological settings and has demonstrated the importance of specific transcription factors in bone development. Three lineages of bone cells, chondrocytes, osteoblasts, and osteoclasts, develop and differentiate according to their distinct developmental programs. These cells go through multiple differentiation stages, which are often regulated by specific transcription factors. In this minireview, we will discuss selected transcription factors that have been demonstrated to critically affect bone cell development. Further study of these molecules will lead to deeper understanding in mechanisms that govern development of bone.

Download Full-text

Mathematical Modeling of Dynamics of Gene Expression Levels Circadian Rhythm

Proceedings of the International Conference on Health and Well-Being in Modern Society (ICHW 2019) ◽

10.2991/ichw-19.2019.4 ◽

2019 ◽

Author(s):

Darna Badgaeva

Keyword(s):

Gene Expression ◽

Mathematical Modeling ◽

Circadian Rhythm ◽

Expression Levels ◽

Modeling Of Dynamics ◽

Gene Expression Levels

Download Full-text

A collection of genetic mouse lines and related tools for inducible and reversible intersectional misexpression

10.1101/754192 ◽

2019 ◽

Author(s):

Elham Ahmadzadeh ◽

N. Sumru Bayin ◽

Xinli Qu ◽

Aditi Singh ◽

Linda Madisen ◽

...

Keyword(s):

Gene Expression ◽

Target Gene ◽

Genetic Manipulation ◽

Cell Types ◽

Biological Processes ◽

Control Of Gene Expression ◽

A Cell ◽

Summary Statement ◽

Spatiotemporal Control ◽

Mouse Lines

AbstractThanks to many advances in genetic manipulation, mouse models have become very powerful in their ability to interrogate biological processes. In order to precisely target expression of a gene of interest to particular cell types, intersectional genetic approaches utilizing two promoter/enhancers unique to a cell type are ideal. Within these methodologies, variants that add temporal control of gene expression are the most powerful. We describe the development, validation and application of an intersectional approach that involves three transgenes, requiring the intersection of two promoter/enhancers to target gene expression to precise cell types. Furthermore, the approach utilizes available lines expressing tTA/rTA to control timing of gene expression based on whether doxycycline is absent or present, respectively. We also show that the approach can be extended to other animal models, using chicken embryos. We generated three mouse lines targeted at the Tigre (Igs7) locus with TRE-loxP-tdTomato-loxP upstream of three genes (p21, DTA and Ctgf) and combined them with Cre and tTA/rtTA lines that target expression to the cerebellum and limbs. Our tools will facilitate unraveling biological questions in multiple fields and organisms.Summary statementAhmadzadeh et al. present a collection of four mouse lines and genetic tools for misexpression-mediated manipulation of cellular activity with high spatiotemporal control, in a reversible manner.

Download Full-text