Molecular and structural lung development in the marsupial model organism Monodelphis domestica

有袋动物模式生物 Monodelphis Domestica 的分子和结构肺发育

• 批准号: 423870628
• 负责人: Dr. Kirsten Ferner
• 金额: --
• 依托单位: Forschungsbereich Dynamik der Natur
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/423870628?language=en
• 关键词: Molecular; structural; lung; development; marsupial

Despite the diversity in respiratory structures, many similarities between the lungs of land vertebrates remain, underlining their common phylogentic origin. This study will be a starting point to evaluate conservatism in the mechanisms regulating the vertebrate lung development (Mammals and Sauropsids). The present project aims to relate structural changes during lung development to the molecular mechanisms that regulate these processes in a basal marsupial species. The gray short-tailed opossum Monodelphis domestica resembles the presumed mammalian morphotype. It provides an alternative model to understand the process of lung development in mammals from an evolutionary point of view. The broncho-alveolar lungs in mammals have evolved to fulfill multiple functions related to terrestrial living and breathing air, however the most important function is to facilitate gas exchange. To achieve this goal, the mammalian lung consists of two branched, tree-like systems—the airways and the vasculature—that develop in a coordinated way from the primary bud stage to the generation of millions of alveolar gas exchange units. The process of lung maturation and the molecular mechanisms involved in lung development were investigated primary in traditional eutherian model organisms. However, to identify the developmental mode in the morphotype of the mammalian lung, the investigation of basal mammalian groups, such as marsupials, is essential. Since the process of lung development takes place largely intrauterine in the eutherian fetus, the structural prerequisites of a functioning lung are difficult to assess. In this regard, marsupials offer a model for studying lung development because the lung maturation is shifted to the postnatal period. An established breeding colony of Monodelphis domestica provides the basis for the ontogenetic stages required for the planned research project. The combination of histological, ultrastructural (TEM, SEM), Micro-CT (3-D reconstruction) techniques allows for a comprehensive morphological and morphometric description of the lung development. The timely and local expression of 11 candidate genes, known to be relevant for lung development, will be analyzed by In situ hybridization (ISH) on histological serial sections. The proposed project will draw a comparison to established eutherian models and questions if the same gene regulatory processes apply to the basal mammalian species or if there are spatial and temporal alterations of gene expression correlated with early lung functionalization. The aim of the project is to identify, locate and confirm factors involved in the maturation of the Monodelphis lung and draw conclusions to basic evolutionary patterns of mammalian lung development.

尽管呼吸结构各不相同，但陆地脊椎动物的肺之间仍有许多相似之处，这强调了它们共同的系统发育起源。本研究将是评估脊椎动物（哺乳动物和蜥脚类）肺发育调控机制中的保守性的一个起点。本项目旨在将肺发育过程中的结构变化与调节这些过程的分子机制联系起来。灰色短尾负鼠（Monodelphis domestica）类似于假定的哺乳动物形态。它提供了一个从进化的角度来理解哺乳动物肺发育过程的替代模型。哺乳动物的支气管肺泡肺已经进化到具有多种与陆地生活和呼吸空气有关的功能，但最重要的功能是促进气体交换。为了达到这个目标，哺乳动物的肺由两个分支的树状系统——气道和血管系统——组成，它们以协调的方式从初级萌芽阶段发展到产生数百万肺泡气体交换单位。本文主要研究了传统真动物模式生物的肺成熟过程和肺发育的分子机制。然而，为了确定哺乳动物肺形态的发育模式，对基础哺乳动物群体（如有袋动物）的研究是必不可少的。由于正常胎儿的肺发育过程主要发生在宫内，因此很难评估肺功能的结构先决条件。在这方面，有袋动物为研究肺发育提供了一个模型，因为肺成熟转移到出生后时期。已建立的家蝇繁殖群为计划研究项目所需的个体发生阶段提供了基础。结合组织学，超微结构（TEM， SEM）， Micro-CT （3d重建）技术，可以对肺发育进行全面的形态学和形态计量学描述。11个候选基因的及时和局部表达，已知与肺发育相关，将通过原位杂交（ISH）对组织学序列切片进行分析。拟议的项目将与已建立的真动物模型进行比较，并询问相同的基因调控过程是否适用于基础哺乳动物物种，或者是否存在与早期肺功能相关的基因表达的时空变化。该项目的目的是识别、定位和确认与单齿兽肺成熟有关的因素，并得出哺乳动物肺发育的基本进化模式的结论。