Regulation of cell fate specification to regenerate complex sensory organs

Some animals have very robust regenerative capacities while others, like humans, have more limited ones. The severity of the injury, as well as the type of the tissue damaged and the animal age, can all impact the regeneration outcomes. Sensory organs are of particular interest to regenerative medicine, as they play a fundamental role in collecting information from our surrounding environment, are composed of multiple cell types, some of these highly specialized, and are directly connected to the central nervous system. Because of this complexity and the scarcity of animals that can robustly regenerate them as adults, we did not have the systems and tools to answer several core questions on this topic. To uncover the molecular mechanisms driving the complete regeneration of sensory organs, we use a freshwater apple snail, Pomacea canaliculata, that has the extraordinary ability to fully regenerate its complex eyes and its cephalic tentacles in only a few weeks. After sequencing the P. canaliculata genome, I developed methods to assess their gene function through CRISPR/Cas9 mutagenesis and mRNA overexpression and collected transcriptomic datasets during the regeneration of the eyes. The proposed project focuses on the mechanisms regulating cell fate specification during the complete regeneration of different complex sensory organs in adult animals. To achieve this, we will take advantage of the possibility to compare the regeneration of two different sensory organs in apple snails: the cephalic tentacles and the eyes. We will take a two-pronged approach: (1) We will establish at what stage the regeneration programs of the two injury paradigms diverge by identifying similarities and differences in the transcriptional responses following eye and tentacle amputation. This will allow us to distinguish between a general regeneration program and organ-specific ones. (2) We will determine the regulatory regions that orchestrate the regeneration of complex sensory organs by building a Gene Regulatory Network for eye and tentacle regeneration and comparing it with regions involved in embryonic development. This will allow us to identify both regeneration-specific and organ-specific regulatory regions that play roles in different moments after the organ amputation. The long-term goal of our laboratory is to mechanistically understand the complete regeneration of complex sensory organs in adult animals, a necessary understanding for planning manipulations to enhance regeneration in other animals. We aim to fully dissect how highly regenerative animals can activate regeneration programs and how developmental genes are reactivated or rewired to participate in these processes. This knowledge will represent a powerful tool to better understand tissue dynamics and plasticity during sensory organ regeneration. By gaining insights into these processes, we can potentially harness the identified mechanisms to advance regenerative medicine. Project Number: 1R35GM162505-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Alice Accorsi | Institution: UNIVERSITY OF CALIFORNIA AT DAVIS, DAVIS, CA | Award Amount: $393,008 | Activity Code: R35 | Study Section: Maximizing Investigators' Research Award C Study Section[MRAC] View on NIH RePORTER: https://reporter.nih.gov/project-details/11272249