Developmental Program
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2021 ◽  
Sushmitha Hegde ◽  
Ashley Sreejan ◽  
Chetan J Gadgil ◽  
Girish S Ratnaparkhi

AbstractIn Drosophila, Toll/NF-κB signalling plays key roles in both animal development and in host defence. The activation, intensity and kinetics of Toll signalling is regulated by post-translational modifications such as phosphorylation, SUMOylation or ubiquitination that target multiple proteins in the Toll/NF-κB cascade.Here, we have generated a CRISPR-Cas9 edited Dorsal (DL) variant that is SUMO conjugation resistant (SCR). Intriguingly, embryos laid by dlSCR mothers overcome dl haploinsufficiency and complete the developmental program. This ability appears to be a result of higher transcriptional activation by DLSCR. In contrast, SUMOylation dampens DL transcriptional activation, ultimately conferring robustness to the dorso-ventral program. In the larval immune response, dlSCR animals show increase in crystal cell numbers, stronger activation of humoral defence genes, high cactus levels and cytoplasmic stabilization of DL:Cactus complexes. A mathematical model that evaluates the contribution of the small fraction of SUMOylated DL (<5%) suggests that it acts to block transcriptional activation, driven primarily by DL that is not SUMO conjugated.Our findings define SUMO conjugation as an important regulator of the Toll signalling cascade, in both development and in host defense. Our results broadly indicate that SUMO attenuates DL at the level of transcriptional activation. Further, we hypothesize that SUMO conjugation of DL may be part of a Ubc9 dependant feedback circuit that restrains Toll/NF-κB signalling.

2021 ◽  
Vol 7 (1) ◽  
Safiye E. Sarper ◽  
Tamami Hirai ◽  
Take Matsuyama ◽  
Shigeru Kuratani ◽  
Koichi Fujimoto

AbstractSymmetry in the arrangement of body parts is a distinctive phylogenetic feature of animals. Cnidarians show both bilateral and radial symmetries in their internal organs, such as gastric pouches and muscles. However, how different symmetries appear during the developmental process remains unknown. Here, we report intraspecific variations in the symmetric arrangement of gastric pouches, muscles, and siphonoglyphs, the Anthozoan-specific organ that drives water into the organism, in D. lineata (Diadumenidae, Actiniaria). We found that the positional arrangement of the internal organs was apparently constrained to either biradial or bilateral symmetries depending on the number of siphonoglyphs. Based on the morphological observations, a mathematical model of internal organ positioning was employed to predict the developmental backgrounds responsible for the biradial and bilateral symmetries. In the model, we assumed that the specification of gastric pouches is orchestrated by lateral inhibition and activation, which results in different symmetries depending on the number of siphonoglyphs. Thus, we propose that a common developmental program can generate either bilateral or biradial symmetries depending on the number of siphonoglyphs formed in the early developmental stages.

2021 ◽  
Harry Klein ◽  
Joseph P Gallagher ◽  
Edgar Demesa-Arevalo ◽  
Maria Jazmin Abraham-Juarez ◽  
Michelle Heeney ◽  

Floral morphology is immensely diverse. One developmental process acting to shape this diversity is growth suppression. For example, grass flowers exhibit extreme diversity in floral sexuality, arising through differential suppression of stamens or carpels. In maize, carpels undergo programmed cell death in half of the flowers initiated in ears and in all flowers in tassels. The HD-ZIP I transcription factor gene GRASSY TILLERS1 (GT1) is one of only a few genes known to regulate this process. To identify additional regulators of carpel suppression, we performed a gt1 enhancer screen, and found a genetic interaction between gt1 and ramosa3 (ra3). RA3 is a classic inflorescence meristem determinacy gene that encodes a trehalose-6-phosphate (T6P) phosphatase (TPP). Dissection of floral development revealed that ra3 single mutants have partially derepressed carpels, whereas gt1; ra3 double mutants have completely derepressed carpels. Surprisingly, gt1 suppresses ra3 inflorescence branching, revealing a role for gt1 in meristem determinacy. Supporting these genetic interactions, GT1 and RA3 proteins colocalize to carpel nuclei in developing flowers. Global expression profiling revealed common genes misregulated in single and double mutant flowers, as well as in derepressed gt1 axillary meristems. Indeed, we found that ra3 enhances gt1 vegetative branching, similar to the roles for the trehalose pathway and GT1 homologs in the eudicots. This functional conservation over ~160 million years of evolution reveals ancient roles for GT1-like genes and the trehalose pathway in regulating axillary meristem suppression, later recruited to mediate carpel suppression. Our findings expose hidden pleiotropy of classic maize genes, and show how an ancient developmental program was redeployed to sculpt floral form.

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0255679
Yin-He Zhao ◽  
Xue-Mei Zhang ◽  
De-Zhu Li

Saururus chinensis is a core member of Saururaceae, an ancient, perianthless (lacking petals or sepals) family of the magnoliids in the Mesangiospermae, which is important for understanding the origin and evolution of early flowers due to its unusual floral composition and petaloid bracts. To compare their transcriptomes, RNA-seq abundance analysis identified 43,463 genes that were found to be differentially expressed in S. chinensis bracts. Of these, 5,797 showed significant differential expression, of which 1,770 were up-regulated and 4,027 down-regulated in green compared to white bracts. The expression profiles were also compared using cDNA microarrays, which identified 166 additional differentially expressed genes. Subsequently, qRT-PCR was used to verify and extend the cDNA microarray results, showing that the A and B class MADS-box genes were up-regulated in the white bracts. Phylogenetic analysis was performed on putative S. chinensis A and B-class of MADS-box genes to infer evolutionary relationships within the A and B-class of MADS-box gene family. In addition, nature selection and protein interactions of B class MADS-box proteins were inferred that B-class genes free from evolutionary pressures. The results indicate that petaloid bracts display anatomical and gene expression features normally associated with petals, as found in petaloid bracts of other species, and support an evolutionarily conserved developmental program for petaloid bracts.

2021 ◽  
Leslie S Babonis ◽  
Camille Enjolras ◽  
Joseph F Ryan ◽  
mark q martindale

Cnidocytes (stinging cells) are an unequivocally novel cell type used by cnidarians (corals, jellyfish, and their kin) to immobilize prey. Although they are known to share a common evolutionary origin with neurons, the developmental program that promoted the emergence of cnidocyte fate is not known. Using functional genomics in the sea anemone, Nematostella vectensis, we show that cnidocytes evolved by suppression of neural fate in a subset of neurons expressing RFamide. We further show that a single regulatory gene, a C2H2-type zinc finger transcription factor (ZNF845), coordinates both the gain of novel (cnidocyte-specific) traits and the inhibition of ancestral (neural) traits during cnidocyte development and that this gene arose by domain shuffling in the stem cnidarian. Thus, we uncover a mechanism by which a truly novel regulatory gene (ZNF845) promoted the origin of a truly novel cell type (cnidocyte) through duplication of an ancestral cell lineage (neuron) and inhibition of its ancestral identity (RFamide).

Nelia Bihun ◽  
Olena Malyna ◽  
Maksym Doichyk ◽  
Ihor Hoian ◽  
Nina Harkavenko ◽  

The article presents a theoretical generalization and a new solution to a scientific problem, expressed in the application of an innovative personal approach to solving the problem of adolescent depressive disorders, the basis of which is the scientific and methodological interpretation of personal development as a defining construct of the system of psychological conditions for the onset of depressive disorders, models of their diagnosis and psychological conditions for overcoming , which ensures the formation of adolescents' ability to effective personal self-regulation and an arbitrary choice of constructive ways of self-realization. The methodological foundations of the study of the personal properties of adolescents with depressive disorders are disclosed, a program for the diagnosis of personal symptoms of depressive disorders of various forms of severity in adolescent schoolchildren is presented; carried out a quantitative and qualitative analysis of the results of the ascertaining experiment on the psychological conditions of the onset of depressive disorders in adolescent schoolchildren and the personality traits of adolescents with depressive disorders; the description of personal phenomenology and symptomatology of depressive disorders in adolescents has been carried out. Theoretical substantiation of the formative experiment is given, the program of correction and optimization of personal development of teenagers as a means of overcoming their depressive disorders is presented, the quantitative and qualitative analysis of the results of its approbation is carried out. A profound restructuring of the structure and qualitative characteristics of the psychological conditions of the personal development of adolescents, their system of personal self-regulation, optimizes the functioning of the mechanism of personal sensitivity - "Ego" -tolerance to destructive influences, is, as the results of the application of the experimental correctional and developmental program, an effective way to overcome depression in adolescents’ disorders.

2021 ◽  
Vol 13 (1) ◽  
L. M. Legault ◽  
K. Doiron ◽  
M. Breton-Larrivée ◽  
A. Langford-Avelar ◽  
A. Lemieux ◽  

Abstract Background Prenatal alcohol exposure is recognized for altering DNA methylation profiles of brain cells during development, and to be part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology.  However, we have negligible information on the effects of alcohol exposure during pre-implantation, the early embryonic window marked with dynamic DNA methylation reprogramming, and on how this may rewire the brain developmental program. Results Using a pre-clinical in vivo mouse model, we show that a binge-like alcohol exposure during pre-implantation at the 8-cell stage leads to surge in morphological brain defects and adverse developmental outcomes during fetal life. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinting control regions, and abnormal de novo DNA methylation profiles in various biological pathways (e.g., neural/brain development). Conclusion These findings support that alcohol-induced DNA methylation programming deviations during pre-implantation could contribute to the manifestation of neurodevelopmental phenotypes associated with FASD.

2021 ◽  
Vol 15 ◽  
Lisiane O. Porciúncula ◽  
Livia Goto-Silva ◽  
Pitia F. Ledur ◽  
Stevens K. Rehen

Over the past years, brain development has been investigated in rodent models, which were particularly relevant to establish the role of specific genes in this process. However, the cytoarchitectonic features, which determine neuronal network formation complexity, are unique to humans. This implies that the developmental program of the human brain and neurological disorders can only partly be reproduced in rodents. Advancement in the study of the human brain surged with cultures of human brain tissue in the lab, generated from induced pluripotent cells reprogrammed from human somatic tissue. These cultures, termed brain organoids, offer an invaluable model for the study of the human brain. Brain organoids reproduce the cytoarchitecture of the cortex and can develop multiple brain regions and cell types. Integration of functional activity of neural cells within brain organoids with genetic, cellular, and morphological data in a comprehensive model for human development and disease is key to advance in the field. Because the functional activity of neural cells within brain organoids relies on cell repertoire and time in culture, here, we review data supporting the gradual formation of complex neural networks in light of cell maturity within brain organoids. In this context, we discuss how the technology behind brain organoids brought advances in understanding neurodevelopmental, pathogen-induced, and neurodegenerative diseases.

2021 ◽  
Aniket Sengupta ◽  
Lena C. Hileman

Abstract BackgroundAn outstanding question in evolutionary biology is how genetic interactions defining novel traits evolve. They may evolve either by de novo assembly of previously non-interacting genes or by en bloc co-option of interactions from other functions. We tested these hypotheses in the context of a novel phenotype—Lamiales flower monosymmetry—defined by a developmental program that relies on regulatory interaction among CYCLOIDEA , RADIALIS , DIVARICATA , and DRIF gene products. In Antirrhinum majus (snapdragon), representing Lamiales, we tested whether components of this program likely function beyond their previously known role in petal and stamen development. In Solanum lycopersicum (tomato), representing Solanales which diverged from Lamiales before the origin of Lamiales floral monosymmetry, we additionally tested for regulatory interactions in this program. ResultsWe found that RADIALIS , DIVARICATA , and DRIF are expressed in snapdragon ovaries and developing fruit, similar to their homologs during tomato fruit development. Additionally, we found that a tomato CYCLOIDEA ortholog positively regulates a tomato RADIALIS ortholog. ConclusionOur results provide preliminary support to the hypothesis that the developmental program defining floral monosymmetry in Lamiales was co-opted en bloc from a function in carpel development. This expands our understanding of novel trait evolution facilitated by co-option of existing regulatory interactions.

Mays Abuhantash ◽  
Emma M. Collins ◽  
Alexander Thompson

Hematopoiesis, the process of blood formation, is controlled by a complex developmental program that involves intrinsic and extrinsic regulators. Blood formation is critical to normal embryonic development and during embryogenesis distinct waves of hematopoiesis have been defined that represent the emergence of hematopoietic stem or progenitor cells. The Class I family of homeobox (HOX) genes are also critical for normal embryonic development, whereby mutations are associated with malformations and deformity. Recently, members of the HOXA cluster (comprising 11 genes and non-coding RNA elements) have been associated with the emergence and maintenance of long-term repopulating HSCs. Previous studies identified a gradient of HOXA expression from high in HSCs to low in circulating peripheral cells, indicating their importance in maintaining blood cell numbers and differentiation state. Indeed, dysregulation of HOXA genes either directly or by genetic lesions of upstream regulators correlates with a malignant phenotype. This review discusses the role of the HOXA cluster in both HSC emergence and blood cancer formation highlighting the need for further research to identify specific roles of these master regulators in normal and malignant hematopoiesis.

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