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

• Applicant: Dr. Kirsten Ferner
• Subject Area: Evolutionary Cell and Developmental Biology (Zoology)
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 423870628

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.

• DFG Programme: Research Grants