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Islet Target Genes Required for Niche Assembly and Formation in Drosophila melanogaster

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2024-12-04

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2026-12-01

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Ledbetter, Sophie I

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Abstract

A particular cell type, known as stem cells, possess a unique capability to self-renew and have the capacity to differentiate into mature cell types. To maintain stem cells, they require signals from a cellular microenvironment called the “niche. The stem cell niche regulates stem cell fate and has the ability to house and regulate a population of stem cells through intricate signaling pathways. Signals transmitted from the niche are important for stem cell self-renewal and cell differentiation signals, and proper signaling requires niche placement in a specific tissue location to polarize the tissue and get regenerated by new cells. Our lab currently studies the Drosophila testis stem cell niche in the male gonads of embryos. Distinct placement of the stem cell niche at apex (tip) of the testis tube organizes stem cells near the apex; cells undergoing differentiation will reside further down the testis tube. The niche forms during late stages of embryogenesis when pro-niche cells begin to migrate to the anterior region of the gonad and assemble the stem cell niche. The gonad niche tilts toward the visceral mesoderm (Vm), which sends Slit and FGF signals. In response to Vm signals, niche cells express the transcription factor islet, which is required for niche cytoskeletal polarization and anterior niche assembly (Anllo and DiNardo, 2022; Anllo et al., 2019). Recent single cell RNA sequencing data predicted Islet target genes that are expressed in the adult niche, and I prioritized testing three of these candidates: btk29A, kon-tiki, and scribble. My goals are to (1) identify if candidate Islet target genes are expressed in the embryonic gonad niche and (2) reveal whether these niche-expressed genes mediate niche assembly and function. My data revealed expressed of all three of these candidates in the niche, show that btk29A is required for niche assembly, and suggest potential roles for scribble, and kon-tiki in niche cells. Future experiments will confirm whether Kon-tiki and Scribble are required for niche assembly. Our understanding of the mechanisms that initially create a compartmentalized stem cell niche during development, in addition to anterior cell movement, will give us a more comprehensive grasp of how the niche is properly formed. These principles will help to clarify concepts about tissue function and development, including the activation of JAK/STAT signaling pathway for stem cell self-renewal, which is translatable to other systems (Leatherman and Di Nardo, 2008).

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