vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-23-87vavilov-3974Research ArticleСИСТЕМНАЯ КОМПЬЮТЕРНАЯ БИОЛОГИЯSYSTEMS COMPUTATIONAL BIOLOGYЦентральный регуляторный контур генной сети морфогенеза механорецепторов дрозофилы: анализ in silicoThe central regulatory circuit in the gene network controlling the morphogenesis of Drosophila mechanoreceptors: an in silico analysishttps://orcid.org/0000-0002-9011-4196БухаринаТ. А.BukharinaT. A.

Новосибирск

Novosibirsk

bukharina@bionet.nsc.ruhttps://orcid.org/0000-0002-9758-3833ГолубятниковВ. П.GolubyatnikovV. P.

Новосибирск

Novosibirsk

ФурманД. П.FurmanD. P.

Новосибирск

Novosibirsk

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian FederationИнститут математики им. С.Л. Соболева Сибирского отделения Российской академии наукРоссияSobolev Institute of Mathematics of the Siberian Branch of the Russian Academy of SciencesRussian Federation202311122023277746754Copyright © Бухарина Т.А., Голубятников В.П., Фурман Д.П., 20232023Бухарина Т.А., Голубятников В.П., Фурман Д.П.Bukharina T.A., Golubyatnikov V.P., Furman D.P.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3974

Выявление механизмов генетического контроля формирования пространственных структур остается одной из актуальных задач биологии развития. Для ее решения используются как экспериментальные, так и теоретические подходы и методы, в том числе методология генных сетей, а также методы математического и компьютерного моделирования. Реконструкция и анализ генных сетей, обеспечивающих становление признака, позволяют интегрировать существующие экспериментальные данные, выявить ключевые звенья и внутрисетевые связи, обеспечивающие функционирование сетей. Для получения динамических характеристик исследуемых систем, предсказания их состояния и поведения привлекаются методы математического и компьютерного моделирования. Одним из примеров пространственной морфологической структуры является щетиночный рисунок дрозофилы со строго определенным расположением на голове и теле мухи его составляющих – механорецепторов (внешних сенсорных органов). Механорецептор развивается из единственной родительской клетки (РКСО), которая выделяется из клеток эктодермы имагинального диска. Ее отличает от окружения наибольшее содержание пронейральных белков (ASC) – продуктов комплекса пронейральных генов achaete-scute (AS-C). Статус РКСО обеспечивается реконструированной нами ранее генной сетью, ключевым объектом которой является комплекс генов AS-C. Контроль активности комплекса осуществляется ее подсетью – центральным регуляторным контуром в составе семи генов (AS-C, hairy, senseless (sens), charlatan (chn), scratch (scrt), phyllopod (phyl), extramacrochaete (emc)) и одноименных белков. Кроме того, в состав центрального регуляторного контура входят вспомогательные белки Daughterless (DA), Groucho (GRO), Ubiquitin (UB) и Seven-in-absentia (SINA). В работе приведены результаты компьютерного моделирования различных режимов функционирования контура. Показано, что клетка детерминируется как РКСО при повышении содержания ASC примерно в два с половиной раза относительно уровня в клетках окружения. Выявлена иерархия влияния мутаций в генах контура на динамику накопления белков ASC. Наиболее значим главный компонент центрального регуляторного контура – AS-C. Мутации, снижающие содержание ASC более чем на 40 %, приводят к запрету выделения родительской клетки сенсорного органа.

Identification of the mechanisms underlying the genetic control of spatial structure formation is among the relevant tasks of developmental biology. Both experimental and theoretical approaches and methods are used for this purpose, including gene network methodology, as well as mathematical and computer modeling. Reconstruction and analysis of the gene networks that provide the formation of traits allow us to integrate the existing experimental data and to identify the key links and intra-network connections that ensure the function of networks. Mathematical and computer modeling is used to obtain the dynamic characteristics of the studied systems and to predict their state and behavior. An example of the spatial morphological structure is the Drosophila bristle pattern with a strictly defined arrangement of its components – mechanoreceptors (external sensory organs) – on the head and body. The mechanoreceptor develops from a single sensory organ parental cell (SOPC), which is isolated from the ectoderm cells of the imaginal disk. It is distinguished from its surroundings by the highest content of proneural proteins (ASC), the products of the achaete-scute proneural gene complex (AS-C). The SOPC status is determined by the gene network we previously reconstructed and the AS-C is the key component of this network. AS-C activity is controlled by its subnetwork – the central regulatory circuit (CRC) comprising seven genes: AS-C, hairy, senseless (sens), charlatan (chn), scratch (scrt), phyllopod (phyl), and extramacrochaete (emc), as well as their respective proteins. In addition, the CRC includes the accessory proteins Daughterless (DA), Groucho (GRO), Ubiquitin (UB), and Seven-in-absentia (SINA). The paper describes the results of computer modeling of different CRC operation modes. As is shown, a cell is determined as an SOPC when the ASC content increases approximately 2.5-fold relative to the level in the surrounding cells. The hierarchy of the effects of mutations in the CRC genes on the dynamics of ASC protein accumulation is clarified. AS-C as the main CRC component is the most significant. The mutations that decrease the ASC content by more than 40 % lead to the prohibition of SOPC segregation.

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The authors declare that there are no conflicts of interest present.