
Ariel Pani
VerifiedUniversity of Virginia · Biology
Active 1997–2026
About
Ariel Pani is an Assistant Professor of Biology at the University of Virginia. He holds a B.A. from Cornell University, where he was a College Scholar in Organismal Biology, earned in 2004, and a Ph.D. in Evolutionary Biology from The University of Chicago in 2013. He completed postdoctoral research at the University of North Carolina at Chapel Hill from 2013 to 2019. His research focuses on developmental biology, cell migration, and organogenesis, with particular emphasis on how active forces maintain the integrity of migrating cells under pressure. Pani's work involves studying molecular mechanisms in model organisms such as C. elegans and hemichordates, contributing to understanding of cell signaling, microtubule dynamics, and tissue organization during development.
Research topics
- Cell biology
- Biology
- Genetics
- Computer Science
- Embedded system
- Operating system
- Computational biology
Selected publications
Polarized SOS activity orchestrates FGF-directed cell migration in vivo
Current Biology · 2026-03-31
articleOpen accessSenior authorDirected cell migration is essential for animal development and homeostasis. Cells often migrate toward or away from sources of secreted proteins that impart spatial information. How cells interpret extracellular signals to navigate to precise destinations is a fundamental question. Receptor tyrosine kinase (RTK) signaling plays critical roles in cell migration, and aberrant RTK pathway activity is implicated in many cancers. Yet how RTKs control cell migration in living animals remains unclear, in part due to the essential, pleiotropic roles of key proteins. To elucidate how RTK signaling directs cell migration in vivo, we systematically dissected the spatial and temporal requirements for key signal transduction and cytoskeletal regulatory proteins in migrating C. elegans muscle progenitors. Cell-type-specific depletion of endogenous proteins revealed that fibroblast growth factor (FGF) receptor (FGFR), growth factor receptor-bound protein 2 (GRB2), Son-of-Sevenless (SOS), and Ras homologs control cell migration independently of their canonical extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and phospholipase C-gamma (PLCγ) effectors. In migrating cells, SOS-1 polarity provided an intracellular readout of the direction of an FGF source, and mislocalizing SOS activity disrupted migration. By contrast, activated Ras was genetically permissive for anterior migration, and an intragenic revertant of Ras/let-60(G13E) revealed that signaling required for cell migration can be uncoupled from Ras-ERK-dependent developmental processes. Regulators of branched actin assembly controlled leading-edge dynamics but were not essential for accurate migration. Our findings provide a novel mechanism for RTK-directed cell migration and highlight the importance of cell-type-specific approaches to elucidate signal transduction mechanisms in their native contexts. This work also introduces a versatile genetic toolkit for dissecting signaling dynamics fundamental to development and disease states.
Development · 2025-08-21 · 1 citations
articleOpen accessSenior authorExtracellular signaling molecules mediate crucial aspects of cell-cell communication and play essential roles in development and homeostasis. Fibroblast growth factors (FGFs) are a family of secreted signaling proteins that can disperse long distances between cells and are often thought to form concentration gradients that encode spatial information. However, we know relatively little about the spatial distribution of FGFs in vivo, and endogenously tagged FGFs move between cells using different mechanisms in zebrafish and flies. We used FGF-dependent migration of C. elegans muscle progenitors called sex myoblasts (SMs) to elucidate FGF dispersal mechanisms and dissect how FGF guides migrating cells. Live imaging of cell dynamics and endogenously tagged FGF combined with membrane tethering and extracellular trapping approaches revealed that endogenous FGF is diffusible in vivo and extracellular dispersal is required for SM migration. Misexpression demonstrated that FGF is a bona fide chemoattractant that orients SMs during a critical window, while an unidentified, short-range signal acts in concert to position SMs precisely. Our finding that an invertebrate FGF is endogenously diffusible suggests that this may be the ancestral mode for FGF dispersal.
bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-14 · 2 citations
preprintOpen accessSenior authorCorrespondingSummary Directed cell migration is essential for animal development, tissue maintenance, regeneration, and disease states. Cells often migrate towards, or away from, sources of secreted signaling proteins that impart spatial information. How migrating cells interpret extracellular signals to orient and navigate within living animals is a fundamental question in biology. Receptor Tyrosine Kinase (RTK) signaling plays critical roles in cell migration, and aberrant RTK pathway activity is a key driver of multiple types of cancers. Yet, how RTKs control cell migration in living animals remains unclear, in part due to essential, pleiotropic roles of key proteins in development. To elucidate how RTK signaling controls cell migration in vivo , we dissected spatial and temporal requirements for key signal transduction and cytoskeletal regulatory proteins using C. elegans muscle progenitor migration as a tractable model. Cell type-specific depletion of endogenously tagged proteins revealed that homologs of FGFR, GRB2, SOS, and Ras control cell migration independently of their canonical ERK, PI3K, Akt, mTOR, and PLCψ effectors. Instead, we found that FGF-dependent, polarized SOS-1 orients migrating cells towards an FGF source, and mislocalizing SOS activity within migrating cells severely disrupts migration independent of ERK. Cell type-specific, gain-of-function experiments demonstrated that activated Ras is largely permissive for anterior migration in this context, and an intragenic revertant identified in a screen for suppressors of activated Ras/let-60 revealed that signal transduction in migrating muscle progenitors can be genetically uncoupled from Ras-ERK-dependent developmental processes. We found that conserved regulators of branched actin assembly control SM protrusive dynamics but are not essential for accurate, FGF-directed migration. Our findings provide a novel mechanism for RTK-directed cell migration in vivo and highlight the importance of cell type-specific approaches to elucidate signal transduction mechanisms in physiologically relevant contexts. Our work also outlines a comprehensive framework for investigating RTK-dependent processes in a multicellular organism and introduces a versatile genetic toolkit for dissecting spatial and temporal signaling dynamics fundamental to development, homeostasis, and disease.
Engineering the <i>C. elegans</i> genome with a nested, self-excising selection cassette
bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-01 · 2 citations
preprintOpen accessSenior authorCorrespondingAbstract C. elegans is a powerful model for dissecting biological processes in vivo . In particular, the ease of generating targeted knock-in alleles makes it possible to visualize and functionally modify endogenous proteins to gain fundamental insights into biological mechanisms. Methods for C. elegans genome engineering typically utilize selectable markers, visual screening for fluorescence, or PCR genotyping to identify successfully edited animals. A common genetic tool known as the Self-Excising Cassette (SEC) combines drug and phenotypic selection, which makes it possible to screen large numbers of progeny rapidly and with minimal hands-on effort. However, N-terminal and internal knock-ins using the SEC cause loss of function until the selectable marker cassette is excised, which makes it impossible to isolate homozygous lines for essential genes prior to SEC excision. To simplify generating knock-ins for essential genes, we developed a Nested, Self-Excising selection Cassette (NSEC) that is located entirely within a synthetic intron and does not interfere with the expression of endogenous, N-terminally-tagged NSEC-fusion proteins. This innovation makes it possible to isolate homozygous lines for N-terminally tagged genes prior to selectable marker excision and allows for a standardized workflow to generate N-terminal and internal tags in any background and without the need for genetic balancers. We designed versions of NSEC that include an optional auxin-inducible degron tag and mTurquoise2, GFP, mStayGold, mNeonGreen, or mScarlet-I fluorescent proteins for experimental flexibility. The NSEC expands our molecular toolbox and enhances the scalability, efficiency, and versatility of C. elegans genome engineering.
bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-19 · 2 citations
preprintOpen accessSenior authorCorrespondingAbstract Extracellular signaling molecules mediate crucial aspects of cell-cell communication and play essential roles in development and homeostasis. Fibroblast Growth Factors (FGFs) are a conserved family of secreted signaling proteins that can disperse long distances between cells and are often thought to form concentration gradients that encode spatial information. However, we know relatively little about the spatial distribution of FGFs in vivo , and endogenously tagged FGFs use different mechanisms to move between cells and form gradients in zebrafish and flies. We used FGF-dependent migration of C. elegans muscle progenitors called sex myoblasts (SMs) as a tractable system to elucidate FGF dispersal mechanisms and dissect how FGF guides migrating cells. Live imaging of cell dynamics and endogenously tagged FGF combined with membrane tethering and extracellular trapping approaches revealed that endogenous FGF is diffusible in vivo and extracellular dispersal is required for SM migration. Misexpression demonstrated FGF is a bona fide chemoattractant that orients SMs during a critical window, while an unidentified, short-range signal acts in concert to precisely position SMs. Our finding that an invertebrate FGF is endogenously diffusible suggests that this may be the ancestral mode for FGF dispersal. Summary Statement Fibroblast Growth Factors (FGFs) are signaling proteins with crucial developmental roles. We demonstrated that a C. elegans FGF homolog is diffusible, and diffusion is required in vivo for cell migration guidance.
2025-03-25
peer-reviewOrganogenesis: How active forces maintain integrity of migrating cells under pressure
Current Biology · 2024-07-01
article1st authorCorrespondingA simple method to dramatically increase C. elegans germline microinjection efficiency
Developmental Biology · 2023 · 10 citations
Senior authorCorresponding- Computer Science
- Biology
- Computational biology
2023-09-26
preprintOpen accessAbstract A growing body of evidence suggests that cell division and basement membrane invasion are mutually exclusive cellular behaviors. How cells switch between proliferative and invasive states is not well understood. Here, we investigated this dichotomy in vivo by examining two cell types in the developing Caenorhabditis elegans somatic gonad that derive from equipotent progenitors, but exhibit distinct cell behaviors: the post-mitotic, invasive anchor cell and the neighboring proliferative, non-invasive ventral uterine (VU) cells. We show that the fates of these cells post-specification are more plastic than previously appreciated and that levels of NHR-67 are important for discriminating between invasive and proliferative behavior. Transcription of nhr-67 is downregulated following post-translational degradation of its direct upstream regulator, HLH-2 (E/Daughterless) in VU cells. In the nuclei of VU cells, residual NHR-67 protein is compartmentalized into discrete punctae that are dynamic over the cell cycle and exhibit liquid-like properties. By screening for proteins that colocalize with NHR-67 punctae, we identified new regulators of uterine cell fate maintenance: homologs of the transcriptional co-repressor Groucho (UNC-37 and LSY-22), as well as the TCF/LEF homolog POP-1. We propose a model in which association of NHR-67 with the Groucho/TCF complex suppresses the default invasive state in non-invasive cells, which complements transcriptional regulation to add robustness to the proliferative-invasive cellular switch in vivo.
PLoS Biology · 2023-09-19 · 13 citations
articleOpen accessCorrespondingHemichordates are an important group for investigating the evolution of bilaterian nervous systems. As the closest chordate outgroup with a bilaterally symmetric adult body plan, hemichordates are particularly informative for exploring the origins of chordates. Despite the importance of hemichordate neuroanatomy for testing hypotheses on deuterostome and chordate evolution, adult hemichordate nervous systems have not been comprehensively described using molecular techniques, and classic histological descriptions disagree on basic aspects of nervous system organization. A molecular description of hemichordate nervous system organization is important for both anatomical comparisons across phyla and for attempts to understand how conserved gene regulatory programs for ectodermal patterning relate to morphological evolution in deep time. Here, we describe the basic organization of the adult hemichordate Saccoglossus kowalevskii nervous system using immunofluorescence, in situ hybridization, and transgenic reporters to visualize neurons, neuropil, and key neuronal cell types. Consistent with previous descriptions, we found the S. kowalevskii nervous system consists of a pervasive nerve plexus concentrated in the anterior, along with nerve cords on both the dorsal and ventral side. Neuronal cell types exhibited clear anteroposterior and dorsoventral regionalization in multiple areas of the body. We observed spatially demarcated expression patterns for many genes involved in synthesis or transport of neurotransmitters and neuropeptides but did not observe clear distinctions between putatively centralized and decentralized portions of the nervous system. The plexus shows regionalized structure and is consistent with the proboscis base as a major site for information processing rather than the dorsal nerve cord. In the trunk, there is a clear division of cell types between the dorsal and ventral cords, suggesting differences in function. The absence of neural processes crossing the basement membrane into muscle and extensive axonal varicosities suggest that volume transmission may play an important role in neural function. These data now facilitate more informed neural comparisons between hemichordates and other groups, contributing to broader debates on the origins and evolution of bilaterian nervous systems.
Recent grants
Dissecting the cell-biological foundations of developmental cell signaling in a living animal
NIH · $2.1M · 2021–2026
NIH · $39k · 2013
Deciphering Roles of Cell Shapes in Signaling
NIH · $52k · 2015–2016
Frequent coauthors
- 37 shared
Christopher J. Lowe
Pacific University
- 21 shared
Bob Goldstein
University of North Carolina at Chapel Hill
- 19 shared
David Q. Matus
University of Freiburg
- 19 shared
John C. Gerhart
University of California, Berkeley
- 18 shared
Mike Wu
Pacific University
- 11 shared
Taylor N. Medwig-Kinney
Stony Brook University
- 11 shared
Daniel J. Dickinson
The University of Texas at Austin
- 11 shared
Colleen A. Morris
University of Nevada, Las Vegas
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