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Developmental Biology: Computational and Experimental Approaches

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 22311

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Guest Editor
Institute of Cytology and Genetics, Novosibirsk State University, Novosibirsk, Russia
Interests: DNA sequence analysis; mutation; single-nucleotide polymorphism (SNP); quantitative sequence-activity relationships; DNA-protein affinity; TATA-binding protein binding site (TATA box); genome-wide prediction in silico; experimental verification; in vitro; in vivo; hereditary disease

Special Issue Information

Dear Colleagues,

Developmental biology investigates ontogenesis that is how step-by-step, single cells (e.g., animal zygotes) turn into multicellular organisms of proper shape, size and structure, which altogether provide all functions during whole life cycle. Molecular mechanisms of both signal transduction and gene regulation networks are elementary basis of ontogenesis within biological organization hierarchy, where they interfere with each other from cellular processes (e.g., differentiation and migration) through morphogenesis up to whole life cycle. As for embryogenesis, among the top achievements of both experimental and computational approaches, which are mutually enriching one another to reconstruct the Drosophila segment polarity gene-network, that is a well-established molecular mechanism of the fruit fly initializing segmentation during 3 hours just after fertilization until embryo of 14 para-segmental units. Respecting to morphogenesis, one of the breakthroughs of combined experimental-computational techniques focused on gene-network of synthesis, diffusion and active transport of auxin in Arabidopsis is certainly the high-resolution 3D-map of cell cycle stages from the root meristem up to the layers of completely differentiated cells. In the matter of life cycle, amongst the greatest successes of the computational models using the experimental signaling network in-between all the 959 cells including all the 302 nerve cells of Caenorhabditis elegans is indisputably accepted a real-time in silico simulator of how nematodes find food and avoid obstacles. In reference to evolutionary limitations within developmental biology, the recent cross-kingdom comparison between animals, plants and fungi integrated the developmental hourglass concept into a modern paradigm of transcriptome ontogenetic switches. Apropos normal development, everything develops normally, whereas developmental abnormalities - premature aging, neurodegeneration, tumorigenesis, induced pluripotent cells, wound healing, post-traumatic repair, regeneration, assisted reproductive technologies, stress-induced epigenetic reprogramming, - which have just become challenges for the post-genome experimental-computational biology, are waiting for their pioneers able to contribute predictive preventive personalized participatory (4P) medicine.

Dr. Mikhail P. Ponomarenko
Guest Editor

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Keywords

  • animal
  • plant
  • fungus
  • biological organization hierarchy
  • evolutionary limitations
  • fertilization
  • zygote
  • cell cycle
  • stem cell
  • meristem
  • cell layer
  • tissue
  • embryo
  • multicellular organism
  • ontogenesis
  • morphogenesis
  • life cycle
  • molecular mechanism
  • signal transduction
  • gene regulation
  • gene-networks
  • cellular process
  • differentiation
  • migration
  • segmentation
  • high-resolution 3D-map
  • real-time in silico simulator
  • developmental hourglass
  • transcriptome ontogenetic switch
  • developmental abnormality
  • premature aging
  • neurodegeneration
  • tumorigenesis
  • atherogenesis
  • autoimmunity
  • induced pluripotent cell
  • wound healing
  • regeneration
  • assisted reproductive technologies
  • epigenetic reprogramming
  • predictive preventive personalized participatory (4P) medicine

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Published Papers (14 papers)

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Editorial

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4 pages, 195 KiB  
Editorial
Developmental Biology: Computational and Experimental Approaches
by Mikhail Ponomarenko
Int. J. Mol. Sci. 2023, 24(13), 10435; https://doi.org/10.3390/ijms241310435 - 21 Jun 2023
Viewed by 1329
Abstract
Developmental biology studies ontogenesis, the individual development of an organism from the time of fertilization in sexual reproduction or its expelling from the maternal organism in asexual reproduction to the end of an organism’s life, with all phenotypical characters typical of this biological [...] Read more.
Developmental biology studies ontogenesis, the individual development of an organism from the time of fertilization in sexual reproduction or its expelling from the maternal organism in asexual reproduction to the end of an organism’s life, with all phenotypical characters typical of this biological species and supporting the normal course of all biochemical processes and morphogenesis [...] Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)

Research

Jump to: Editorial

17 pages, 11884 KiB  
Article
Amyloid Fibrils of the s36 Protein Modulate the Morphogenesis of Drosophila melanogaster Eggshell
by Anna A. Valina, Vera A. Siniukova, Tatyana A. Belashova, Alexander A. Kanapin, Anastasia A. Samsonova, Alexey E. Masharsky, Anna N. Lykholay, Svetlana A. Galkina, Sergey P. Zadorsky and Alexey P. Galkin
Int. J. Mol. Sci. 2024, 25(23), 12499; https://doi.org/10.3390/ijms252312499 - 21 Nov 2024
Viewed by 253
Abstract
Drosophila melanogaster is the oldest classic model object in developmental genetics. It may seem that various structures of the fruit fly at all developmental stages have been well studied and described. However, recently we have shown that some specialized structures of the D. [...] Read more.
Drosophila melanogaster is the oldest classic model object in developmental genetics. It may seem that various structures of the fruit fly at all developmental stages have been well studied and described. However, recently we have shown that some specialized structures of the D. melanogaster eggshell contain an amyloid fibril network. Here, we demonstrate that this amyloid network is formed by the chorionic protein s36. The s36 protein colocalizes with the amyloid-specific dyes Congo Red and Thioflavin S in the micropyle, dorsal appendages, and pillars. The fibrils of s36 obtained from the eggs demonstrate amyloid properties. In the context of the CG33223 gene deletion, the s36 protein is produced but is not detected in the eggshell. The absence of amyloid fibrils of s36 in the eggshell disrupts the endochorion morphology and blocks the development of the micropyle, dorsal appendages, and pillars, leading to sterility. Our data show for the first time that amyloid fibrils are essential for morphogenesis modulation. We suggest that attachment of follicle cells to the s36 extracellular fibrils triggers signaling to enable subsequent cellular divisions needed for building the specialized eggshell structures. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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17 pages, 6817 KiB  
Article
Higher Steroid Production in the Right Adrenal Gland Compared to the Left One in db/db Mice, a Model of Type 2 Diabetic Obesity
by Rengui Saxu, Qiming Luo, Yong Yang and Harvest F. Gu
Int. J. Mol. Sci. 2024, 25(19), 10658; https://doi.org/10.3390/ijms251910658 - 3 Oct 2024
Viewed by 592
Abstract
Vertebrates exhibit a left–right asymmetry from the central structures to the peripheral paired endocrine organs. However, the asymmetries in paired endocrine glands and the pathological consequences of such asymmetries remain largely unknown. The adrenal gland constitutes a pair of peripheral end organs in [...] Read more.
Vertebrates exhibit a left–right asymmetry from the central structures to the peripheral paired endocrine organs. However, the asymmetries in paired endocrine glands and the pathological consequences of such asymmetries remain largely unknown. The adrenal gland constitutes a pair of peripheral end organs in the neuroendocrine system, responsible for producing steroid hormones under stimuli. In the present study, the lateralized asymmetry of left and right adrenal glands in leptin receptor-deficit db/db mice was investigated. First, a morphological and histological examination showed that adrenal mass and adrenal cortex volume in db/db mice were significantly higher than in non-diabetic control mice. Then, adrenal transcriptomic and serum metabolomic analyses were performed. Adrenal steroid profiling showed that the levels of corticosterone and aldosterone in the right adrenal gland of db/db mice were two times higher than in the left one. The expression of multiple genes related to adrenal regeneration and innervation in db/db mice was reduced in contrast to the increased steroid hormone secretion. Furthermore, an examination of morphogens in asymmetric adrenal development revealed a significant differential expression of Shh and its receptor gene Ptch1. In conclusion, the present study has provided evidence that a superior steroidogenesis exists in the right adrenal gland of db/db mice and suggested that Shh signaling may play an important role in asymmetric adrenal responses in type 2 diabetes and its complications. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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31 pages, 15716 KiB  
Article
Effect of Short-Term Restraint Stress on the Hypothalamic Transcriptome Profiles of Rats with Inherited Stress-Induced Arterial Hypertension (ISIAH) and Normotensive Wistar Albino Glaxo (WAG) Rats
by Dmitry Yu. Oshchepkov, Yulia V. Makovka, Larisa A. Fedoseeva, Alisa A. Seryapina, Arcady L. Markel and Olga E. Redina
Int. J. Mol. Sci. 2024, 25(12), 6680; https://doi.org/10.3390/ijms25126680 - 18 Jun 2024
Cited by 1 | Viewed by 951
Abstract
Emotional stress is one of the health risk factors in the modern human lifestyle. Stress exposure can provoke the manifestation of various pathological conditions, one of which is a sharp increase in the blood pressure level. In the present study, we analyzed changes [...] Read more.
Emotional stress is one of the health risk factors in the modern human lifestyle. Stress exposure can provoke the manifestation of various pathological conditions, one of which is a sharp increase in the blood pressure level. In the present study, we analyzed changes in the transcriptome profiles of the hypothalamus of hypertensive ISIAH and normotensive WAG rats exposed to a single short-term restraint stress (the rat was placed in a tight wire-mesh cage for 2 h). This type of stress can be considered emotional stress. The functional annotation of differentially expressed genes allowed us to identify the most significantly altered biological processes in the hypothalamus of hypertensive and normotensive rats. The study made it possible to identify a group of genes that describe a general response to stress, independent of the rat genotype, as well as a hypothalamic response to stress specific to each strain. The alternatively changing expression of the Npas4 (neuronal PAS domain protein 4) gene, which is downregulated in the hypothalamus of the control WAG rats and induced in the hypothalamus of hypertensive ISIAH rats, is suggested to be the key event for understanding inter-strain differences in the hypothalamic response to stress. The stress-dependent ISIAH strain-specific induction of Fos and Jun gene transcription may play a crucial role in neuronal activation in this rat strain. The data obtained can be potentially useful in the selection of molecular targets for the development of pharmacological approaches to the correction of stress-induced pathologies related to neuronal excitability, taking into account the hypertensive status of the patients. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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39 pages, 11069 KiB  
Article
Molecular Basis for the Involvement of Mammalian Serum Albumin in the AGE/RAGE Axis: A Comprehensive Computational Study
by Daria A. Belinskaia, Richard O. Jenkins and Nikolay V. Goncharov
Int. J. Mol. Sci. 2024, 25(6), 3204; https://doi.org/10.3390/ijms25063204 - 11 Mar 2024
Viewed by 1085
Abstract
In mammals, glycated serum albumin (gSA) contributes to the pathogenesis of many metabolic diseases by activating the receptors (RAGE) for advanced glycation end products (AGEs). Many aspects of the gSA–RAGE interaction remain unknown. The purpose of the present paper was to study the [...] Read more.
In mammals, glycated serum albumin (gSA) contributes to the pathogenesis of many metabolic diseases by activating the receptors (RAGE) for advanced glycation end products (AGEs). Many aspects of the gSA–RAGE interaction remain unknown. The purpose of the present paper was to study the interaction of glycated human albumin (gHSA) with RAGE using molecular modeling methods. Ten models of gHSA modified with different lysine residues to carboxymethyl-lysines were prepared. Complexes of gHSA–RAGE were obtained by the macromolecular docking method with subsequent molecular dynamics simulation (MD). According to the MD, the RAGE complexes with gHSA glycated at Lys233, Lys64, Lys525, Lys262 and Lys378 are the strongest. Three-dimensional models of the RAGE dimers with gHSA were proposed. Additional computational experiments showed that the binding of fatty acids (FAs) to HSA does not affect the ability of Lys525 (the most reactive lysine) to be glycated. In contrast, modification of Lys525 reduces the affinity of albumin for FA. The interspecies differences in the molecular structure of albumin that may affect the mechanism of the gSA–RAGE interaction were discussed. The obtained results will help us to learn more about the molecular basis for the involvement of serum albumin in the AGE/RAGE axis and improve the methodology for studying cellular signaling pathways involving RAGE. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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18 pages, 3815 KiB  
Article
Loss of ERβ Disrupts Gene Regulation in Primordial and Primary Follicles
by Eun Bee Lee, V. Praveen Chakravarthi, Ryan Mohamadi, Vinesh Dahiya, Kevin Vo, Anamika Ratri, Patrick E. Fields, Courtney A. Marsh and M. A. Karim Rumi
Int. J. Mol. Sci. 2024, 25(6), 3202; https://doi.org/10.3390/ijms25063202 - 11 Mar 2024
Cited by 1 | Viewed by 1252
Abstract
Loss of ERβ increases primordial follicle growth activation (PFGA), leading to premature ovarian follicle reserve depletion. We determined the expression and gene regulatory functions of ERβ in dormant primordial follicles (PdFs) and activated primary follicles (PrFs) using mouse models. PdFs and PrFs were [...] Read more.
Loss of ERβ increases primordial follicle growth activation (PFGA), leading to premature ovarian follicle reserve depletion. We determined the expression and gene regulatory functions of ERβ in dormant primordial follicles (PdFs) and activated primary follicles (PrFs) using mouse models. PdFs and PrFs were isolated from 3-week-old Erβ knockout (Erβnull) mouse ovaries, and their transcriptomes were compared with those of control Erβfl/fl mice. We observed a significant (≥2-fold change; FDR p-value ≤ 0.05) deregulation of approximately 5% of genes (866 out of 16,940 genes, TPM ≥ 5) in Erβnull PdFs; ~60% (521 out of 866) of the differentially expressed genes (DEGs) were upregulated, and 40% were downregulated, indicating that ERβ has both transcriptional enhancing as well as repressing roles in dormant PdFs. Such deregulation of genes may make the Erβnull PdFs more susceptible to increased PFGA. When the PdFs undergo PFGA and form PrFs, many new genes are activated. During PFGA of Erβfl/fl follicles, we detected a differential expression of ~24% genes (4909 out of 20,743; ≥2-fold change; FDR p-value ≤ 0.05; TPM ≥ 5); 56% upregulated and 44% downregulated, indicating the gene enhancing and repressing roles of Erβ-activated PrFs. In contrast, we detected a differential expression of only 824 genes in Erβnull follicles during PFGA (≥2-fold change; FDR p-value ≤ 0.05; TPM ≥ 5). Moreover, most (~93%; 770 out of 824) of these DEGs in activated Erβnull PrFs were downregulated. Such deregulation of genes in Erβnull activated follicles may impair their inhibitory role on PFGA. Notably, in both Erβnull PdFs and PrFs, we detected a significant number of epigenetic regulators and transcription factors to be differentially expressed, which suggests that lack of ERβ either directly or indirectly deregulates the gene expression in PdFs and PrFs, leading to increased PFGA. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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11 pages, 1895 KiB  
Communication
BestCRM: An Exhaustive Search for Optimal Cis-Regulatory Modules in Promoters Accelerated by the Multidimensional Hash Function
by Igor V. Deyneko
Int. J. Mol. Sci. 2024, 25(3), 1903; https://doi.org/10.3390/ijms25031903 - 5 Feb 2024
Cited by 1 | Viewed by 910
Abstract
The concept of cis-regulatory modules located in gene promoters represents today’s vision of the organization of gene transcriptional regulation. Such modules are a combination of two or more single, short DNA motifs. The bioinformatic identification of such modules belongs to so-called NP-hard problems [...] Read more.
The concept of cis-regulatory modules located in gene promoters represents today’s vision of the organization of gene transcriptional regulation. Such modules are a combination of two or more single, short DNA motifs. The bioinformatic identification of such modules belongs to so-called NP-hard problems with extreme computational complexity, and therefore, simplifications, assumptions, and heuristics are usually deployed to tackle the problem. In practice, this requires, first, many parameters to be set before the search, and second, it leads to the identification of locally optimal results. Here, a novel method is presented, aimed at identifying the cis-regulatory elements in gene promoters based on an exhaustive search of all the feasible modules’ configurations. All required parameters are automatically estimated using positive and negative datasets. To be computationally efficient, the search is accelerated using a multidimensional hash function, allowing the search to complete in a few hours on a regular laptop (for example, a CPU Intel i7, 3.2 GH, 32 Gb RAM). Tests on an established benchmark and real data show better performance of BestCRM compared to the available methods according to several metrics like specificity, sensitivity, AUC, etc. A great practical advantage of the method is its minimum number of input parameters—apart from positive and negative promoters, only a desired level of module presence in promoters is required. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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15 pages, 3428 KiB  
Article
Cancer Associated PRDM9: Implications for Linking Genomic Instability and Meiotic Recombination
by Paris Ladias, Georgios S. Markopoulos, Charilaos Kostoulas, Ioanna Bouba, Sofia Markoula and Ioannis Georgiou
Int. J. Mol. Sci. 2023, 24(22), 16522; https://doi.org/10.3390/ijms242216522 - 20 Nov 2023
Viewed by 1610
Abstract
The PR domain-containing 9 or PRDM9 is a gene recognized for its fundamental role in meiosis, a process essential for forming reproductive cells. Recent findings have implicated alterations in the PRDM9, particularly its zinc finger motifs, in the onset and progression of cancer. [...] Read more.
The PR domain-containing 9 or PRDM9 is a gene recognized for its fundamental role in meiosis, a process essential for forming reproductive cells. Recent findings have implicated alterations in the PRDM9, particularly its zinc finger motifs, in the onset and progression of cancer. This association is manifested through genomic instability and the misregulation of genes critical to cell growth, proliferation, and differentiation. In our comprehensive study, we harnessed advanced bioinformatic mining tools to delve deep into the intricate relationship between PRDM9F and cancer. We analyzed 136,752 breakpoints and found an undeniable association between specific PRDM9 motifs and the occurrence of double-strand breaks, a phenomenon evidenced in every cancer profile examined. Utilizing R statistical querying and the Regioner package, 55 unique sequence variations of PRDM9 were statistically correlated with cancer, from a pool of 1024 variations. A robust analysis using the Enrichr tool revealed prominent associations with various cancer types. Moreover, connections were noted with specific phenotypic conditions and molecular functions, underlining the pervasive influence of PRDM9 variations in the biological spectrum. The Reactome tool identified 25 significant pathways associated with cancer, offering insights into the mechanistic underpinnings linking PRDM9 to cancer progression. This detailed analysis not only confirms the pivotal role of PRDM9 in cancer development, but also unveils a complex network of biological processes influenced by its variations. The insights gained lay a solid foundation for future research aimed at deciphering the mechanistic pathways of PRDM9, offering prospects for targeted interventions and innovative therapeutic approaches in cancer management. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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19 pages, 1506 KiB  
Article
The New General Biological Property of Stem-like Tumor Cells (Part II: Surface Molecules, Which Belongs to Distinctive Groups with Particular Functions, Form a Unique Pattern Characteristic of a Certain Type of Tumor Stem-like Cells)
by Daria D. Petrova, Evgeniya V. Dolgova, Anastasia S. Proskurina, Genrikh S. Ritter, Vera S. Ruzanova, Yaroslav R. Efremov, Ekaterina A. Potter, Svetlana S. Kirikovich, Evgeniy V. Levites, Oleg S. Taranov, Alexandr A. Ostanin, Elena R. Chernykh, Nikolay A. Kolchanov and Sergey S. Bogachev
Int. J. Mol. Sci. 2022, 23(24), 15800; https://doi.org/10.3390/ijms232415800 - 13 Dec 2022
Cited by 3 | Viewed by 1685
Abstract
An ability of poorly differentiated cells of different genesis, including tumor stem-like cells (TSCs), to internalize extracellular double-stranded DNA (dsDNA) fragments was revealed in our studies. Using the models of Krebs-2 murine ascites carcinoma and EBV-induced human B-cell lymphoma culture, we demonstrated that [...] Read more.
An ability of poorly differentiated cells of different genesis, including tumor stem-like cells (TSCs), to internalize extracellular double-stranded DNA (dsDNA) fragments was revealed in our studies. Using the models of Krebs-2 murine ascites carcinoma and EBV-induced human B-cell lymphoma culture, we demonstrated that dsDNA internalization into the cell consists of several mechanistically distinct phases. The primary contact with cell membrane factors is determined by electrostatic interactions. Firm contacts with cell envelope proteins are then formed, followed by internalization into the cell of the complex formed between the factor and the dsDNA probe bound to it. The key binding sites were found to be the heparin-binding domains, which are constituents of various cell surface proteins of TSCs—either the C1q domain, the collagen-binding domain, or domains of positively charged amino acids. These results imply that the interaction between extracellular dsDNA fragments and the cell, as well as their internalization, took place with the involvement of glycocalyx components (proteoglycans/glycoproteins (PGs/GPs) and glycosylphosphatidylinositol-anchored proteins (GPI-APs)) and the system of scavenger receptors (SRs), which are characteristic of TSCs and form functional clusters of cell surface proteins in TSCs. The key provisions of the concept characterizing the principle of organization of the “group-specific” cell surface factors of TSCs of various geneses were formulated. These factors belong to three protein clusters: GPs/PGs, GIP-APs, and SRs. For TSCs of different tumors, these clusters were found to be represented by different members with homotypic functions corresponding to the general function of the cluster to which they belong. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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18 pages, 2421 KiB  
Article
Mother–Fetus Immune Cross-Talk Coordinates “Extrinsic”/“Intrinsic” Embryo Gene Expression Noise and Growth Stability
by Tatyana Ivanovna Babochkina, Ludmila Alekseevna Gerlinskaya, Margarita Vladimirovna Anisimova, Galina Vladimirovna Kontsevaya, Natalia Aleksandrovna Feofanova, Aliya Konstantinovna Stanova, Mikhail Pavlovich Moshkin and Yuri Mikhailovich Moshkin
Int. J. Mol. Sci. 2022, 23(20), 12467; https://doi.org/10.3390/ijms232012467 - 18 Oct 2022
Cited by 2 | Viewed by 1686
Abstract
Developmental instability (DI) is thought to be inversely related to a capacity of an organism to buffer its development against random genetic and environmental perturbations. DI is represented by a trait’s inter- and intra-individual variabilities. The inter-individual variability (inversely referred to as canalization) [...] Read more.
Developmental instability (DI) is thought to be inversely related to a capacity of an organism to buffer its development against random genetic and environmental perturbations. DI is represented by a trait’s inter- and intra-individual variabilities. The inter-individual variability (inversely referred to as canalization) indicates the capability of organisms to reproduce a trait from individual to individual. The intra-individual variability reflects an organism’s capability to stabilize a trait internally under the same conditions, and, for symmetric traits, it is expressed as fluctuating asymmetry (FA). When representing a trait as a random variable conditioned on environmental fluctuations, it is clear that, in statistical terms, the DI partitions into “extrinsic” (canalization) and “intrinsic” (FA) components of a trait’s variance/noise. We established a simple statistical framework to dissect both parts of a symmetric trait variance/noise using a PCA (principal component analysis) projection of the left/right measurements on eigenvectors followed by GAMLSS (generalized additive models for location scale and shape) modeling of eigenvalues. The first eigenvalue represents “extrinsic” and the second—“intrinsic” DI components. We applied this framework to investigate the impact of mother–fetus major histocompatibility complex (MHC)-mediated immune cross-talk on gene expression noise and developmental stability. We showed that “intrinsic” gene noise for the entire transcriptional landscape could be estimated from a small subset of randomly selected genes. Using a diagnostic set of genes, we found that allogeneic MHC combinations tended to decrease “extrinsic” and “intrinsic” gene noise in C57BL/6J embryos developing in the surrogate NOD-SCID and BALB/c mothers. The “intrinsic” gene noise was negatively correlated with growth (embryonic mass) and the levels of placental growth factor (PLGF), but not vascular endothelial growth factor (VEGF). However, it was positively associated with phenotypic growth instability and noise in PLGF. In mammals, the mother–fetus MHC interaction plays a significant role in development, contributing to the fitness of the offspring. Our results demonstrate that a positive impact of distant MHC combinations on embryonic growth could be mediated by the reduction of “intrinsic” gene noise followed by the developmental stabilization of growth. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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17 pages, 1106 KiB  
Article
Transcription Factors as Important Regulators of Changes in Behavior through Domestication of Gray Rats: Quantitative Data from RNA Sequencing
by Dmitry Oshchepkov, Irina Chadaeva, Rimma Kozhemyakina, Svetlana Shikhevich, Ekaterina Sharypova, Ludmila Savinkova, Natalya V. Klimova, Anton Tsukanov, Victor G. Levitsky and Arcady L. Markel
Int. J. Mol. Sci. 2022, 23(20), 12269; https://doi.org/10.3390/ijms232012269 - 14 Oct 2022
Cited by 8 | Viewed by 2367
Abstract
Studies on hereditary fixation of the tame-behavior phenotype during animal domestication remain relevant and important because they are of both basic research and applied significance. In model animals, gray rats Rattus norvegicus bred for either an enhancement or reduction in defensive response to [...] Read more.
Studies on hereditary fixation of the tame-behavior phenotype during animal domestication remain relevant and important because they are of both basic research and applied significance. In model animals, gray rats Rattus norvegicus bred for either an enhancement or reduction in defensive response to humans, for the first time, we used high-throughput RNA sequencing to investigate differential expression of genes in tissue samples from the tegmental region of the midbrain in 2-month-old rats showing either tame or aggressive behavior. A total of 42 differentially expressed genes (DEGs; adjusted p-value  <  0.01 and fold-change  >  2) were identified, with 20 upregulated and 22 downregulated genes in the tissue samples from tame rats compared with aggressive rats. Among them, three genes encoding transcription factors (TFs) were detected: Ascl3 was upregulated, whereas Fos and Fosb were downregulated in tissue samples from the brains of tame rats brain. Other DEGs were annotated as associated with extracellular matrix components, transporter proteins, the neurotransmitter system, signaling molecules, and immune system proteins. We believe that these DEGs encode proteins that constitute a multifactorial system determining the behavior for which the rats have been artificially selected. We demonstrated that several structural subtypes of E-box motifs—known as binding sites for many developmental TFs of the bHLH class, including the ASCL subfamily of TFs—are enriched in the set of promoters of the DEGs downregulated in the tissue samples of tame rats’. Because ASCL3 may act as a repressor on target genes of other developmental TFs of the bHLH class, we hypothesize that the expression of TF gene Ascl3 in tame rats indicates longer neurogenesis (as compared to aggressive rats), which is a sign of neoteny and domestication. Thus, our domestication model shows a new function of TF ASCL3: it may play the most important role in behavioral changes in animals. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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16 pages, 33222 KiB  
Article
Formation of Unique Placental Seed Capsules in the Maturation Process of the Tomato Fruit
by Inna A. Chaban, Alexander A. Gulevich and Ekaterina N. Baranova
Int. J. Mol. Sci. 2022, 23(19), 11101; https://doi.org/10.3390/ijms231911101 - 21 Sep 2022
Cited by 3 | Viewed by 3408
Abstract
The morphological and anatomical study of the seed formation features in a juicy tomato fruit was carried out. The ovules, which form on the placenta, have been shown to be gradually enveloped by the protrusions of placental tissue that arises simultaneously with them. [...] Read more.
The morphological and anatomical study of the seed formation features in a juicy tomato fruit was carried out. The ovules, which form on the placenta, have been shown to be gradually enveloped by the protrusions of placental tissue that arises simultaneously with them. As a result of this process, each seed is enclosed in an individual capsule. These seed capsules have been shown in vivo to be airtight and air-filled. Tomato seeds, as has been shown in this study, develop inside these capsules until the full maturity of the fruit and do not come into contact with the detached and moldered cells of the placenta protrusions, which convert into a gel (pulp). Using scanning electron microscopy, it was possible to reveal the details of a ribbon-like “pubescence” formation of the tomato seed, as well as to understand the mechanism of cracking of the outer layer cells in the seed coat, associated with the detection of calcium oxalate crystals in these cells. The unique outer layer of the tomato seed coat seems to play the role of a scaffold that maintains a constant volume of the protective capsule. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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9 pages, 1016 KiB  
Article
In Silico Study of piRNA Interactions with the SARS-CoV-2 Genome
by Aigul Akimniyazova, Oxana Yurikova, Anna Pyrkova, Aizhan Rakhmetullina, Togzhan Niyazova, Alma-Gul Ryskulova and Anatoliy Ivashchenko
Int. J. Mol. Sci. 2022, 23(17), 9919; https://doi.org/10.3390/ijms23179919 - 31 Aug 2022
Cited by 7 | Viewed by 1909
Abstract
A prolonged pandemic with numerous human casualties requires a rapid search for means to control the various strains of SARS-CoV-2. Since only part of the human population is affected by coronaviruses, there are probably endogenous compounds preventing the spread of these viral pathogens. [...] Read more.
A prolonged pandemic with numerous human casualties requires a rapid search for means to control the various strains of SARS-CoV-2. Since only part of the human population is affected by coronaviruses, there are probably endogenous compounds preventing the spread of these viral pathogens. It has been shown that piRNA (PIWI-interacting RNAs) interact with the mRNA of human genes and can block protein synthesis at the stage of translation. Estimated the effects of piRNA on SARS-CoV-2 genomic RNA (gRNA) in silico. A cluster of 13 piRNA binding sites (BS) in the SARS-CoV-2 gRNA region encoding the oligopeptide was identified. The second cluster of BSs 39 piRNAs also encodes the oligopeptide. The third cluster of 24 piRNA BS encodes the oligopeptide. Twelve piRNAs were identified that strongly interact with the gRNA. Based on the identified functionally important endogenous piRNAs, synthetic piRNAs (spiRNAs) are proposed that will suppress the multiplication of the coronavirus even more strongly. These spiRNAs and selected endogenous piRNAs have little effect on human 17494 protein-coding genes, indicating a low probability of side effects. The piRNA and spiRNA selection methodology created for the control of SARS-CoV-2 (NC_045512.2) can be used to control all strains of SARS-CoV-2. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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Article
Plant_SNP_TATA_Z-Tester: A Web Service That Unequivocally Estimates the Impact of Proximal Promoter Mutations on Plant Gene Expression
by Dmitry Rasskazov, Irina Chadaeva, Ekaterina Sharypova, Karina Zolotareva, Bato Khandaev, Petr Ponomarenko, Nikolay Podkolodnyy, Natalya Tverdokhleb, Oleg Vishnevsky, Anton Bogomolov, Olga Podkolodnaya, Ludmila Savinkova, Elena Zemlyanskaya, Vadimir Golubyatnikov, Nikolay Kolchanov and Mikhail Ponomarenko
Int. J. Mol. Sci. 2022, 23(15), 8684; https://doi.org/10.3390/ijms23158684 - 4 Aug 2022
Cited by 9 | Viewed by 1780
Abstract
Synthetic targeted optimization of plant promoters is becoming a part of progress in mainstream postgenomic agriculture along with hybridization of cultivated plants with wild congeners, as well as marker-assisted breeding. Therefore, here, for the first time, we compiled all the experimental data—on mutational [...] Read more.
Synthetic targeted optimization of plant promoters is becoming a part of progress in mainstream postgenomic agriculture along with hybridization of cultivated plants with wild congeners, as well as marker-assisted breeding. Therefore, here, for the first time, we compiled all the experimental data—on mutational effects in plant proximal promoters on gene expression—that we could find in PubMed. Some of these datasets cast doubt on both the existence and the uniqueness of the sought solution, which could unequivocally estimate effects of proximal promoter mutation on gene expression when plants are grown under various environmental conditions during their development. This means that the inverse problem under study is ill-posed. Furthermore, we found experimental data on in vitro interchangeability of plant and human TATA-binding proteins allowing the application of Tikhonov’s regularization, making this problem well-posed. Within these frameworks, we created our Web service Plant_SNP_TATA_Z-tester and then determined the limits of its applicability using those data that cast doubt on both the existence and the uniqueness of the sought solution. We confirmed that the effects (of proximal promoter mutations on gene expression) predicted by Plant_SNP_TATA_Z-tester correlate statistically significantly with all the experimental data under study. Lastly, we exemplified an application of Plant_SNP_TATA_Z-tester to agriculturally valuable mutations in plant promoters. Full article
(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)
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