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Biology subjects

Anllo, L.

Publications and source records attributed to Anllo, L..

5 recordsLinked to original sources

Polarized F-actin establishes cell interactions required for the formation of a stem cell niche

Lifelong stem cells are maintained by a cellular microenvironment called the niche, which enables tissue homeostasis. Proper niche construction is essential for persistent function, but studying niche formation is challenged by the inaccessibility of most niches to in vivo visualization during development. Innovations imaging the Drosophila testis are now allowing investigation of niche inception. F-actin polarizes to precise cell interfaces during testis niche assembly. Yet it is unknown whether polarization directs niche cell motility, or reflects adhesive sorting in response to formation of niche cell contacts. By adapting a method to optogenetically manipulate cortical F-actin via disruption of Rho1, we interrogate the role for cytoskeletal polarization during niche formation with tissue and temporal specificity. Rho1-mediated disruption of F-actin polarization caused defects in niche anterior assembly and architecture. Also, fewer cells adopted bona fide niche identity, given diminished Fas3, N-Cadherin, and Islet. These disrupted niches fail in signaling to germ cells to establish stem cell identity. We reveal that polarized F-actin is crucial for establishing cell contacts to form a functional niche, and to maintain cell identity in the developing tissue. Summary StatementOptogenetic cortical localization of cytoskeletal disruptors reveals tissue and temporal specific requirements for F-actin polarization in establishing a functional stem cell niche.

developmental biology↗

Tbx1 ortholog org-1 is required to establish testis stem cell niche identity in Drosophila

Stem cells require signals from a cellular microenvironment known as the niche that regulates identity, location, and division of stem cells. Niche cell identity must be properly specified during development to form a tissue capable of functioning in the adult. Here, we show that the Tbx1 ortholog org1 is expressed in Drosophila testis niche cells in response to Slit and FGF signals. org1 is expressed during niche development and is required to specify niche cell identity. org1 mutants specified fewer niche cells, and those cells showed disruption of niche-specific markers, including loss of the niche adhesion protein Fas3 and reduced hedgehog expression. We found that org1 expression in somatic gonadal precursors is capable of inducing formation of additional niche cells. Disrupted niche identity in org1 mutants resulted in niche assembly and functionality defects. We find the conserved transcription factor islet is expressed in response to org1 and show that islet functions downstream to mediate niche identity and assembly. This work identifies a novel role for org1 in niche establishment. Summary StatementSpecification of niche identity is crucial to establish a functional stem cell microenvironment. Using a translatable model, we show that niche expression of org1 influences islet to specify niche identity.

developmental biology↗

The Drosophila hematopoietic niche assembles through collective cell migration controlled by neighbor tissues and Slit-Robo signaling

Niches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established. To address this, we investigated the formation of a genetically tractable niche, the Drosophila Posterior Signaling Center (PSC), the assembly of which had not been previously explored. This niche controls hematopoietic progenitors of the lymph gland (LG). PSC cells were previously shown to be specified laterally in the embryo, but ultimately reside dorsally, at the LG posterior. Here, using live-imaging, we show that PSC cells migrate as a tight collective and associate with multiple tissues during their trajectory to the LG posterior. We find that Slit emanating from two extrinsic sources, visceral mesoderm and cardioblasts, is required for the PSC to remain a collective, and for its attachment to cardioblasts during migration. Without proper Slit-Robo signaling, PSC cells disperse, form aberrant contacts, and ultimately fail to reach their stereotypical position near progenitors. Our work characterizes a novel example of niche formation and identifies an extrinsic signaling relay that controls precise niche positioning. Impact StatementA new example of niche formation is provided which reveals the mode of niche cell migration, implicates extrinsic sources that deliver positional information, and uncovers the signaling pathway required for the precise, stereotypical positioning of the niche.

developmental biology↗

An actomyosin network organizes niche morphology and responds to feedback from recruited stem cells

SummaryStem cells often rely on signals from a niche, which in many tissues adopts a precise morphology. What remains elusive is how niches are formed, and how morphology impacts function. To address this, we leverage the Drosophila gonadal niche, which affords genetic tractability and live-imaging. We have previously shown mechanisms dictating niche cell migration to their appropriate position within the gonad, and the resultant consequences on niche function. Here, we show that once positioned, niche cells robustly polarize filamentous actin (F-actin) and Non-muscle Myosin II (MyoII) towards neighboring germ cells. Actomyosin tension along the niche periphery generates a highly reproducible smoothened contour. Without contractility, niches are misshapen and exhibit defects in their ability to regulate germline stem cell behavior. We additionally show that germ cells aid in polarizing MyoII within niche cells, and that extrinsic input is required for niche morphogenesis and function. Our work reveals a feedback mechanism where stem cells shape the niche that guides their behavior.

developmental biology↗

Visceral mesoderm signaling regulates assembly position and function of the Drosophila testis niche

Tissue homeostasis often requires a properly placed niche to support stem cells. Morphogenetic processes that position a niche are just being described. For the Drosophila testis we recently showed that pro niche cells, specified at disparate positions during early gonadogenesis, must assemble into one collective at the anterior of the gonad. We now find that Slit and FGF signals emanating from adjacent visceral mesoderm regulate assembly. In response to signaling, niche cells express islet, which we find is also required for niche assembly. Without signaling, niche cells specified furthest from the anterior are unable to migrate, remaining dispersed. Function of such niches is severely disrupted, with niche cells evading cell cycle quiescence, compromised in their ability to signal the incipient stem cell pool, and failing to orient stem cell divisions properly. Our work identifies both extrinsic signaling and intrinsic responses required for proper assembly and placement of the testis niche.

developmental biology↗