RUI: Role of the Endoplasmic Reticulum in mediating cell fate

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A major step during development in multicellular life is the generation of cell diversity. Specifically, the task of cells adopting a specific shape and function is essential towards development of the adult body plan and formation of tissues in multicellular organisms. This is a highly conserved process among multicellular creatures and involves an unequal or asymmetric partitioning of factors during cell division to allow cells to adopt different fates (e.g. to become neurons or become skin). There has been significant progress in understanding the distribution of these factors; however, the regulation of movement and the selection of these determinants and how they are passed to daughter cells is still poorly understood. The Principal Investigator (PI) has formed a model in which cell fate-determining factors are organized and distributed during cell division by the Endoplasmic Reticulum (ER), the largest compartment in the cell involved in protein folding and distribution. The objectives of this project are to define a pathway for the transport and correct establishment of cell-fate determinants during cell division, and to characterize the role of the ER in the generation of cell diversity. In addition, the PI will provide opportunities to engage a diverse student population and promote peer mentorship, thereby broadening participating in science. The outcomes of the project will help close a gap of knowledge regarding how cell fate is determined, and to provide a broader understanding for the generation of cell diversity during development.The generation of cell diversity is a highly conserved mechanism and involves the asymmetric partitioning of factors during cell division. Over the past 30 years, several cell fate determinants have been identified, including cell fate determinants that are partitioned apically or basally during mitosis leading to the daughter cells adopting different cell fates. Despite the considerable knowledge regarding the factors involved in cell fate selection, there is little known regarding the transport, localization, and organization of these cell fate determinants along the division plane during mitosis. Preliminary data from the PI’s laboratory identified the highly conserved Endoplasmic Reticulum (ER) integral membrane protein, Jagunal (Jagn) as being partitioned asymmetrically in pro-neural cells during Drosophila melanogaster embryogenesis. The PI’s central hypothesis is that the Jagn-mediated asymmetric division of the ER acts as a scaffold for organization and transport of transcriptional machinery involving the basal cell fate determinants towards the diversification of cell types in the central nervous system. The PI will test this hypothesis in vivo by examining neuroblast division in the Drosophila melanogaster larval brain by means of super-resolution confocal microscopy, and determine which cell fate outcomes are dependent on Jagn. The PI’s work will deepen our understanding of cell fate selection and outline the role of the ER in the generation of cell diversity.This research is funded by the Cellular Dynamics and Function cluster in the Division of Molecular and Cellular Biosciences in the Directorate of Biological Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.