Developmental Regulation by Nutritional Control via Spatial Metabolic Preferences

• Applicant: Dr. Aissam Ikmi
• Subject Area: Developmental Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 567925519

Nutritional cues are fundamental regulators of organismal development, yet the mechanisms by which these signals are integrated into metabolic control remain poorly understood. In particular, the interplay between spatial metabolic fuel preferences and developmental outcomes represents a critical gap in our knowledge. In bilaterian models (e.g., mouse, zebrafish, and Drosophila), different tissues exhibit distinct metabolic programs, with some maintaining metabolic flexibility while others rely on constrained fuel preferences. For example, the liver can shift between glucose and fat metabolism depending on nutrient availability, whereas the heart primarily oxidizes fatty acids, and the brain depends on glycolysis. While metabolic flexibility permits adaptation to fluctuating nutritional conditions, restricted metabolic programs often lead to additional costs. Their persistence therefore raises fundamental questions regarding their evolutionary origins and functional roles. This project investigates how a constrained metabolic program regulates tentacle development in the cnidarian Nematostella vectensis, providing insights into the evolutionary and functional significance of metabolic specialization. Our preliminary findings indicate that Nematostella tentacles maintain a restricted metabolic program, preferentially utilizing fatty acid oxidation (FAO) as their dominant energy source, irrespective of nutrient availability. Importantly, inhibition of FAO disrupts tentacle development without affecting overall body growth, demonstrating the dependence of tentacle development on this energy source. Our project has three aims. (1) Validation of spatially constrained metabolic programs in Nematostella by employing spatial transcriptomics, metabolomics, and flux analysis. This approach will allow us to construct a detailed metabolic atlas that differentiates glycolytic regions from FAO-dominant regions. (2) Understanding the short-term role of FAO in tentacle morphogenesis. We will assess the impact of FAO inhibition on tentacle budding and dissect the involvement of key energy-sensing pathways, including AMPK and mTOR. Additionally, we will test whether an inducible genetic system that enhances glycolytic flux can rescue the developmental deficits caused by FAO inhibition. (3) Examination of the long-term role of fat storage as a developmental switch. By manipulating fat storage through targeted gene knockdowns (e.g., perilipin), we will link fat reserve thresholds to the initiation of tentacle development. We will also investigate the role of the fat-preferring program in controlling the stringency of this connection. By leveraging an early-branching metazoan with a simplified body plan, our findings will bridge gaps in our understanding of metabo-developmental interplay and illuminate the evolutionary significance of metabolic specialization in animal systems.

• DFG Programme: Research Grants