A novel expression domain of extradenticle underlies the evolutionary developmental origin of the chelicerate patella.

Neofunctionalization of duplicated gene copies is thought to be an important process underlying the origin of evolutionary novelty and provides an elegant mechanism for the origin of new phenotypic traits. One putative case where a new gene copy has been linked to a novel morphological trait is the origin of the arachnid patella, a taxonomically restricted leg segment. In spiders, the origin of this segment has been linked to the origin of the paralog dachshund-2 , suggesting that a new gene facilitated the expression of a new trait. However, various arachnid groups that possess patellae do not have a copy of dachshund-2 , disfavoring the direct link between gene origin and trait origin. We investigated the developmental genetic basis for patellar patterning in the harvestman Phalangium opilio , which lacks dachshund-2 . Here, we show that the harvestman patella is established by a novel expression domain of the transcription factor extradenticle . Leveraging this definition of patellar identity, we surveyed targeted groups across chelicerate phylogeny to assess when this trait evolved. We show that a patellar homolog is present in Pycnogonida (sea spiders) and various arachnid orders, suggesting a single origin of the patella in the ancestor of Chelicerata. A potential loss of the patella is observed in Ixodida. Our results suggest that the modification of an ancient gene, rather than the neofunctionalization of a new gene copy, underlies the origin of the patella. Broadly, this work underscores the value of comparative data and broad taxonomic sampling when testing hypotheses in evolutionary developmental biology.

AIMS for wildlife: Developing an automated interactive monitoring system to integrate real-time movement and environmental data for true adaptive management.

To effectively manage species and habitats at multiple scales, population and land managers require rapid information on wildlife use of managed areas and responses to landscape conditions and management actions. GPS tracking studies of wildlife are particularly informative to species ecology, habitat use, and conservation. Combining GPS data with administrative data and a diverse suite of remotely sensed, geo-referenced environmental (e.g., climatic) data, would more comprehensively inform how animals interact with and utilize habitats and ecosystems and our goal was to create a conceptual model for a system that would accomplish this - the 'Automated Interactive Monitoring System (AIMS) for Wildlife'. Our objective for this study was to develop a Customized Wildlife Report (CWR) - the first AIMS for Wildlife deliverable product. CWRs collate and summarize our 8-year GPS tracking dataset of ∼11 million locations from 1338 individual (16 species) avifauna and make actionable, real-time data on animal movements and trends in a specific area of interest available to managers and stakeholders for rapid application in day-to-day management. The CWR exemplar presented in this paper was developed to address needs identified by habitat managers of Sacramento National Wildlife Refuge and illustrates the highly specific, information offered and how it contributes to assessing the efficacy of conservation actions while allowing for near real-time adaptive management. The report can be easily customized for any of the thousands of wildlife refuges or regional areas of interest in the United States, emphasizing the broad application of an animal movement data stream. Utilizing diverse, extensive telemetry data streams through scientific collaboration can aid managers and conservation stakeholders with short and long-term research and conservation planning and help address a cadre of issues from local-scale habitat management to improving the understanding of landscape level impacts like drought, wildfire, and climate change on wildlife populations.

Ventral striatum dopamine release encodes unique properties of visual stimuli in mice.

The mesolimbic dopamine system is an evolutionarily conserved set of brain circuits that play a role in attention, appetitive behavior, and reward processing. In this circuitry, ascending dopaminergic projections from the ventral midbrain innervate targets throughout the limbic forebrain, such as the ventral striatum/nucleus accumbens (NAc). Dopaminergic signaling in the NAc has been widely studied for its role in behavioral reinforcement, reward prediction error encoding, and motivational salience. Less well characterized is the role of dopaminergic neurotransmission in the response to surprising or alerting sensory events. To address this, we used the genetically encoded dopamine sensor dLight1 and fiber photometry to explore the ability of striatal dopamine release to encode the properties of salient sensory stimuli in mice, such as threatening looming discs. Here, we report that lateral NAc (LNAc) dopamine release encodes the rate and magnitude of environmental luminance changes rather than the visual stimulus threat level. This encoding is highly sensitive, as LNAc dopamine could be evoked by light intensities that were imperceptible to human experimenters. We also found that light-evoked dopamine responses are wavelength-dependent at low irradiances, independent of the circadian cycle, robust to previous exposure history, and involve multiple phototransduction pathways. Thus, we have further elaborated the mesolimbic dopamine system's ability to encode visual information in mice, which is likely relevant to a wide body of scientists employing light sources or optical methods in behavioral research involving rodents.

Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system.

Brainstem olivocochlear neurons (OCNs) modulate the earliest stages of auditory processing through feedback projections to the cochlea and have been shown to influence hearing and protect the ear from sound-induced damage. Here, we used single-nucleus sequencing, anatomical reconstructions, and electrophysiology to characterize murine OCNs during postnatal development, in mature animals, and after sound exposure. We identified markers for known medial (MOC) and lateral (LOC) OCN subtypes, and show that they express distinct cohorts of physiologically relevant genes that change over development. In addition, we discovered a neuropeptide-enriched LOC subtype that produces Neuropeptide Y along with other neurotransmitters. Throughout the cochlea, both LOC subtypes extend arborizations over wide frequency domains. Moreover, LOC neuropeptide expression is strongly upregulated days after acoustic trauma, potentially providing a sustained protective signal to the cochlea. OCNs are therefore poised to have diffuse, dynamic effects on early auditory processing over timescales ranging from milliseconds to days.

Just as our pupils dilate or shrink depending on the amount of light available to our eyes, our ears adjust their sensitivity based on the sound environment we encounter. Evidence suggests that a group of cells known as olivocochlear neurons (OCNs for short) may be involved in this process. These cells are located in the brainstem but project into the cochlea, the inner ear structure that converts sound waves into the electrical impulses relayed to the brain. OCNs may mediate how sounds are detected and encoded "at the source." Historically, OCNs have been divided into two groups (medial or lateral OCNs) based on different morphologies and roles in hearing. For instance, medial OCNs are thought to protect our ears against loud sounds by sending molecular signals to the inner ear cells that amplify certain auditory signals. However, it remains difficult to disentangle the precise function of the different types of OCNs, in part because scientists still lack markers that would allow them to distinguish between medial and lateral cells simply based on genetic activity. Frank et al. aimed to eliminate this bottleneck by identifying which genes were switched on and to what degree in individual mouse medial and lateral OCNs; this was done throughout development and after exposure to loud noises. The experiments uncovered a range of genetic markers for medial and lateral OCNs, showing that these cells switch on different sets of genes relevant to their role over development. This gene expression data also revealed that two distinct groups of lateral OCNs exist, one of which is characterised by the production of large amounts of neuropeptides, a type of chemical messenger that can modulate neural circuit activity. Further work in both developing and adult mice showed that this production is shaped by the activity of the cells, with the neuropeptide levels increasing when the animals are exposed to damaging levels of noise. This change lasts for several days, suggesting that such an experience can have long-lasting effects on how the brain provides feedback to the ear. Overall, the results by Frank et al. will help to better identify and characterize the different types of OCNs and the role that they have in hearing. By uncovering the chemical messengers that mediate the response to loud noises, this research may contribute to a better understanding of how to prevent or reduce hearing loss.

Morphological and sensorimotor phenotypes in a zebrafish CHARGE syndrome model are domain-dependent.

CHARGE syndrome is a heterogeneous disorder characterized by a spectrum of defects affecting multiple tissues and behavioral difficulties such as autism, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, and sensory deficits. Most CHARGE cases arise from de novo, loss-of-function mutations in chromodomain-helicase-DNA-binding-protein-7 (CHD7). CHD7 is required for processes such as neuronal differentiation and neural crest cell migration, but how CHD7 affects neural circuit function to regulate behavior is unclear. To investigate the pathophysiology of behavioral symptoms in CHARGE, we established a mutant chd7 zebrafish line that recapitulates multiple CHARGE phenotypes including ear, cardiac, and craniofacial defects. Using a panel of behavioral assays, we found that chd7 mutants have specific auditory and visual behavior deficits that are independent of defects in sensory structures. Mauthner cell-dependent short-latency acoustic startle responses are normal in chd7 mutants, while Mauthner-independent long-latency responses are reduced. Responses to sudden decreases in light are also reduced in mutants, while responses to sudden increases in light are normal, suggesting that the retinal OFF pathway may be affected. Furthermore, by analyzing multiple chd7 alleles we observed that the penetrance of morphological and behavioral phenotypes is influenced by genetic background but that it also depends on the mutation location, with a chromodomain mutation causing the highest penetrance. This pattern is consistent with analysis of a CHARGE patient dataset in which symptom penetrance was highest in subjects with mutations in the CHD7 chromodomains. These results provide new insight into the heterogeneity of CHARGE and will inform future work to define CHD7-dependent neurobehavioral mechanisms.

'When the bedbugs come, that's another problem': exploring the lived experiences of bedbug infestations among low-income older adults and service providers who support them.

AIMS: Older adults in low-income housing communities are more vulnerable to bedbug infestations. Prior research, however, has predominately focused on the effectiveness of integrated pest-management strategies, with little attention given to the lived experiences of tenants struggling with infestations. We used a qualitative approach to explore what it is like to live with and treat bedbug infestations from the perspectives of low-income older adults and service providers. METHODS: Participants included low-income older adults (n = 58) and service providers (n = 58) who offer supports directly in the buildings. Semi-structured qualitative interviews and focus groups were used to explore the challenges of preparing and treating units for bedbugs, and examine how bedbugs impact access to support services. RESULTS: Bedbugs were a widespread issue, and underlying physical, mental, social, and financial challenges made it difficult for older tenants to prepare their units and access treatment. Tenants also faced bedbug stigma from community services, as many were unwilling to provide services in infested units. Although some service providers utilized strategies to minimize exposure, many were concerned these strategies created additional stigma. CONCLUSION: Our findings highlight an urgent need to increase public health funding to support older adults with the costs of bedbug elimination and to enhance pest-management strategies through partnerships with health and social service agencies to improve outcomes for older adults.

Pathways for avian influenza virus spread: GPS reveals wild waterfowl in commercial livestock facilities and connectivity with the natural wetland landscape.

Zoonotic diseases are of considerable concern to the human population and viruses such as avian influenza (AIV) threaten food security, wildlife conservation and human health. Wild waterfowl and the natural wetlands they use are known AIV reservoirs, with birds capable of virus transmission to domestic poultry populations. While infection risk models have linked migration routes and AIV outbreaks, there is a limited understanding of wild waterfowl presence on commercial livestock facilities, and movement patterns linked to natural wetlands. We documented 11 wild waterfowl (three Anatidae species) in or near eight commercial livestock facilities in Washington and California with GPS telemetry data. Wild ducks used dairy and beef cattle feed lots and facility retention ponds during both day and night suggesting use for roosting and foraging. Two individuals (single locations) were observed inside poultry facility boundaries while using nearby wetlands. Ducks demonstrated high site fidelity, returning to the same areas of habitats (at livestock facilities and nearby wetlands), across months or years, showed strong connectivity with surrounding wetlands, and arrived from wetlands up to 1251 km away in the week prior. Telemetry data provides substantial advantages over observational data, allowing assessment of individual movement behaviour and wetland connectivity that has significant implications for outbreak management. Telemetry improves our understanding of risk factors for waterfowl-livestock virus transmission and helps identify factors associated with coincident space use at the wild waterfowl-domestic livestock interface. Our research suggests that even relatively small or isolated natural and artificial water or food sources in/near facilities increases the likelihood of attracting waterfowl, which has important consequences for managers attempting to minimize or prevent AIV outbreaks. Use and interpretation of telemetry data, especially in near-real-time, could provide key information for reducing virus transmission risk between waterfowl and livestock, improving protective barriers between wild and domestic species, and abating outbreaks.

Diversity of developing peripheral glia revealed by single-cell RNA sequencing.

The peripheral nervous system responds to a wide variety of sensory stimuli, a process that requires great neuronal diversity. These diverse neurons are closely associated with glial cells originating from the neural crest. However, the molecular nature and diversity among peripheral glia are not understood. Here, we used single-cell RNA sequencing to profile developing and mature glia from somatosensory dorsal root ganglia and auditory spiral ganglia. We found that glial precursors (GPs) in these two systems differ in their transcriptional profiles. Despite their unique features, somatosensory and auditory GPs undergo convergent differentiation to generate molecularly uniform myelinating and non-myelinating Schwann cells. By contrast, somatosensory and auditory satellite glial cells retain system-specific features. Lastly, we identified a glial signature gene set, providing new insights into commonalities among glia across the nervous system. This survey of gene expression in peripheral glia constitutes a resource for understanding functions of glia across different sensory modalities.

Informing wetland management with waterfowl movement and sanctuary use responses to human-induced disturbance.

Long-term environmental management to prevent waterfowl population declines is informed by ecology, movement behavior and habitat use patterns. Extrinsic factors, such as human-induced disturbance, can cause behavioral changes which may influence movement and resource needs, driving variation that affects management efficacy. To better understand the relationship between human-based disturbance and animal movement and habitat use, and their potential effects on management, we GPS tracked 15 dabbling ducks in California over ~4-weeks before, during and after the start of a recreational hunting season in October/November 2018. We recorded locations at 2-min intervals across three separate 24-h tracking phases: Phase 1) two weeks before the start of the hunting season (control (undisturbed) movement); Phase 2) the hunting season opening weekend; and Phase 3) a hunting weekend two weeks after opening weekend. We used GLMM models to analyze variation in movement and habitat use under hunting pressure compared with 'normal' observed patterns prior to commencement of hunting. We also compared responses to differing levels of disturbance related to the time of day (high - shooting/~daytime); moderate - non-lethal (~crepuscular); and low - night). During opening weekend flight (% time and distance) more than doubled during moderate and low disturbance and increased by ~50% during high disturbance compared with the pre-season weekend. Sanctuary use tripled during moderate and low disturbance and increased ~50% during high disturbance. Two weeks later flight decreased in all disturbance levels but was only less than the pre-season levels during high disturbance. In contrast, sanctuary use only decreased at night, although not to pre-season levels, while daytime doubled from ~45% to >80%. Birds adjust rapidly to disturbance and our results have implications for energetics models that estimate population food requirements. Management would benefit from reassessing the juxtaposition of essential sanctuary and feeding habitats to optimize wetland management for waterfowl.

Insights into the genomic evolution of insects from cricket genomes.

Most of our knowledge of insect genomes comes from Holometabolous species, which undergo complete metamorphosis and have genomes typically under 2 Gb with little signs of DNA methylation. In contrast, Hemimetabolous insects undergo the presumed ancestral process of incomplete metamorphosis, and have larger genomes with high levels of DNA methylation. Hemimetabolous species from the Orthopteran order (grasshoppers and crickets) have some of the largest known insect genomes. What drives the evolution of these unusual insect genome sizes, remains unknown. Here we report the sequencing, assembly and annotation of the 1.66-Gb genome of the Mediterranean field cricket Gryllus bimaculatus, and the annotation of the 1.60-Gb genome of the Hawaiian cricket Laupala kohalensis. We compare these two cricket genomes with those of 14 additional insects and find evidence that hemimetabolous genomes expanded due to transposable element activity. Based on the ratio of observed to expected CpG sites, we find higher conservation and stronger purifying selection of methylated genes than non-methylated genes. Finally, our analysis suggests an expansion of the pickpocket class V gene family in crickets, which we speculate might play a role in the evolution of cricket courtship, including their characteristic chirping.

Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model.

Conventional cancer chemotherapies are not fully efficacious and do not target tumors, leading to significant treatment-related morbidities. A number of genetically attenuated cancer-targeting bacteria are being developed to safely target tumors in vivo. Here we report the toxicological, tumor-targeting, and efficacy profiles of Salmonella enterica serovar Typhimurium CRC2631 in a syngeneic and autochthonous TRAMP model of aggressive prostate cancer. CRC2631 preferentially colonize primary and metastatic tumors in the TRAMP animals. In addition, longitudinal whole genome sequencing studies of CRC2631 recovered from prostate tumor tissues demonstrate that CRC2631 is genetically stable. Moreover, tumor-targeted CRC2631 generates an anti-tumor immune response. Combination of CRC2631 with checkpoint blockade reduces metastasis burden. Collectively, these findings demonstrate a potential for CRC2631 in cancer immunotherapy strategies.

Quantifying drought's influence on moist soil seed vegetation in California's Central Valley through remote sensing.

California's Central Valley, USA is a critical component of the Pacific Flyway despite loss of more than 90% of its wetlands. Moist soil seed (MSS) wetland plants are now produced by mimicking seasonal flooding in managed wetlands to provide an essential food resource for waterfowl. Managers need MSS plant area and productivity estimates to support waterfowl conservation, yet this remains unknown at the landscape scale. Also the effects of recent drought on MSS plants have not been quantified. We generated Landsat-derived estimates of extents and productivity (seed yield or its proxy, the green chlorophyll index) of major MSS plants including watergrass (Echinochloa crusgalli) and smartweed (Polygonum spp.) (WGSW), and swamp timothy (Crypsis schoenoides) (ST) in all Central Valley managed wetlands from 2007 to 2017. We tested the effects of water year, land ownership and region on plant area and productivity with a multifactor nested analysis of variance. For the San Joaquin Valley, we explored the association between water year and water supply, and we developed metrics to support management decisions. MSS plant area maps were based on a support vector machine classification of Landsat phenology metrics (2017 map overall accuracy: 89%). ST productivity maps were created with a linear regression model of seed yield (n = 68, R2  = 0.53, normalized RMSE = 10.5%). The Central Valley-wide estimated area for ST in 2017 was 32,369 ha (29,845-34,893 ha 95% CI), and 13,012 ha (11,628-14,396 ha) for WGSW. Mean ST seed yield ranged from 577 kg/ha in the Delta Basin to 365 kg/ha in the San Joaquin Basin. WGSW area and ST seed yield decreased while ST area increased in critical drought years compared to normal water years (Scheffe's test, P < 0.05). Greatest ST area increases occurred in the Sacramento Valley (~75%). Voluntary water deliveries increased in normal water years, and ST seed yield increased with water supply. Z scores of ST seed yield can be used to evaluate wetland performance and aid resource allocation decisions. Updated maps will support habitat monitoring, conservation planning and water management in future years, which are likely to face greater uncertainty in water availability with climate change.

Hox genes limit germ cell formation in the short germ insect Gryllus bimaculatus.

Hox genes are conserved transcription factor-encoding genes that specify the identity of body regions in bilaterally symmetrical animals. In the cricket Gryllus bimaculatus, a member of the hemimetabolous insect group Orthoptera, the induction of a subset of mesodermal cells to form the primordial germ cells (PGCs) is restricted to the second through the fourth abdominal segments (A2 to A4). In numerous insect species, the Hox genes Sex-combs reduced (Scr), Antennapedia (Antp), Ultrabithorax (Ubx), and abdominal-A (abd-A) jointly regulate the identities of middle and posterior body segments, suggesting that these genes may restrict PGC formation to specific abdominal segments in G. bimaculatus Here we show that reducing transcript levels of some or all of these Hox genes results in supernumerary and/or ectopic PGCs, either individually or in segment-specific combinations, suggesting that the role of these Hox genes is to limit PGC development with respect to their number, segmental location, or both. These data provide evidence of a role for this ancient group of genes in PGC development.

Spatiotemporal distribution of glia in and around the developing mouse optic tract.

In the developing mouse optic tract, retinal ganglion cell (RGC) axon position is organized by topography and laterality (i.e., eye-specific or ipsi- and contralateral segregation). Our lab previously showed that ipsilaterally projecting RGCs are segregated to the lateral aspect of the developing optic tract and found that ipsilateral axons self-fasciculate to a greater extent than contralaterally projecting RGC axons in vitro. However, the full complement of axon-intrinsic and -extrinsic factors mediating eye-specific segregation in the tract remain poorly understood. Glia, which are known to express several guidance cues in the visual system and regulate the navigation of ipsilateral and contralateral RGC axons at the optic chiasm, are natural candidates for contributing to eye-specific pre-target axon organization. Here, we investigate the spatiotemporal expression patterns of both putative astrocytes (Aldh1l1+ cells) and microglia (Iba1+ cells) in the embryonic and neonatal optic tract. We quantified the localization of ipsilateral RGC axons to the lateral two-thirds of the optic tract and analyzed glia position and distribution relative to eye-specific axon organization. While our results indicate that glial segregation patterns do not strictly align with eye-specific RGC axon segregation in the tract, we identify distinct spatiotemporal organization of both Aldh1l1+ cells and microglia in and around the developing optic tract. These findings inform future research into molecular mechanisms of glial involvement in RGC axon growth and organization in the developing retinogeniculate pathway.

Early segmentation in the mite Archegozetes longisetosus reveals conserved and derived aspects of chelicerate development.

The arthropod body plan is comprised of several repeating segments along the anteroposterior body axis. This high degree of conservation, however, obfuscates the wide degree of underlying developmental variation present across and within arthropod groups. In chelicerates, the arthropod clade containing mites, spiders, scorpions, and horseshoe crabs, development is the most similar at the stages following early germ band segmentation. Comparative studies of chelicerate segmentation prior to these events, however, remain scarce. In order to elucidate and identify possible shared and derived aspects of chelicerate segmentation, we followed the early prosomal (anterior) segmentation in the model mite Archegozetes longisetosus using the expression of the conserved segmental marker hedgehog (hh). Our data indicate that the ancestral chelicerate likely utilized the gene hedgehog in a group of cells surrounding the germ disc. We also provide evidence that chelicerate segmentation, albeit via the conserved "short/intermediate germ" mode, progresses differently in the prosoma between Archegozetes and spiders and thus early, anterior segmentation in chelicerates is heterochronic.

Eye-specific segregation and differential fasciculation of developing retinal ganglion cell axons in the mouse visual pathway.

Prior to forming and refining synaptic connections, axons of projection neurons navigate long distances to their targets. While much is known about guidance cues for axon navigation through intermediate choice points, whether and how axons are organized within tracts is less clear. Here we analyze the organization of retinal ganglion cell (RGC) axons in the developing mouse retinogeniculate pathway. RGC axons are organized by both eye-specificity and topography in the optic nerve and tract: ipsilateral RGC axons are segregated from contralateral axons and are offset laterally in the tract relative to contralateral axon topographic position. To identify potential cell-autonomous factors contributing to the segregation of ipsilateral and contralateral RGC axons in the visual pathway, we assessed their fasciculation behavior in a retinal explant assay. Ipsilateral RGC neurites self-fasciculate more than contralateral neurites in vitro and maintain this difference in the presence of extrinsic chiasm cues. To further probe the role of axon self-association in circuit formation in vivo, we examined RGC axon organization and fasciculation in an EphB1-/- mutant, in which a subset of ipsilateral RGC axons aberrantly crosses the midline but targets the ipsilateral zone in the dorsal lateral geniculate nucleus on the opposite side. Aberrantly crossing axons retain their association with ipsilateral axons in the contralateral tract, indicating that cohort-specific axon affinity is maintained independently of guidance signals present at the midline. Our results provide a comprehensive assessment of RGC axon organization in the retinogeniculate pathway and suggest that axon self-association contributes to pre-target axon organization.

Shh-ushing Midline Crossing through Remote Protein Transport.

Shh contributes to neural circuit formation with different mechanisms. In this issue, Peng and colleagues (2018) identify a novel trans-axonal mechanism by which Shh derived from contralateral projecting retinal ganglion cells prevents midline crossing of Boc-expressing ipsilateral axons at the optic chiasm.

SoxC Transcription Factors Promote Contralateral Retinal Ganglion Cell Differentiation and Axon Guidance in the Mouse Visual System.

Transcription factors control cell identity by regulating diverse developmental steps such as differentiation and axon guidance. The mammalian binocular visual circuit is comprised of projections of retinal ganglion cells (RGCs) to ipsilateral and contralateral targets in the brain. A transcriptional code for ipsilateral RGC identity has been identified, but less is known about the transcriptional regulation of contralateral RGC development. Here we demonstrate that SoxC genes (Sox4, 11, and 12) act on the progenitor-to-postmitotic transition to implement contralateral, but not ipsilateral, RGC differentiation, by binding to Hes5 and thus repressing Notch signaling. When SoxC genes are deleted in postmitotic RGCs, contralateral RGC axons grow poorly on chiasm cells in vitro and project ipsilaterally at the chiasm midline in vivo, and Plexin-A1 and Nr-CAM expression in RGCs is downregulated. These data implicate SoxC transcription factors in the regulation of contralateral RGC differentiation and axon guidance.

Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila.

The noncanonical Frizzled/planar cell polarity (PCP) pathway regulates establishment of polarity within the plane of an epithelium to generate diversity of cell fates, asymmetric, but highly aligned structures, or to orchestrate the directional migration of cells during convergent extension during vertebrate gastrulation. In Drosophila, PCP signaling is essential to orient actin wing hairs and to align ommatidia in the eye, in part by coordinating the movement of groups of photoreceptor cells during ommatidial rotation. Importantly, the coordination of PCP signaling with changes in the cytoskeleton is essential for proper epithelial polarity. Formins polymerize linear actin filaments and are key regulators of the actin cytoskeleton. Here, we show that the diaphanous-related formin, Frl, the single fly member of the FMNL (formin related in leukocytes/formin-like) formin subfamily affects ommatidial rotation in the Drosophila eye and is controlled by the Rho family GTPase Cdc42. Interestingly, we also found that frl mutants exhibit an axon growth phenotype in the mushroom body, a center for olfactory learning in the Drosophila brain, which is also affected in a subset of PCP genes. Significantly, Frl cooperates with Cdc42 and another formin, DAAM, during mushroom body formation. This study thus suggests that different formins can cooperate or act independently in distinct tissues, likely integrating various signaling inputs with the regulation of the cytoskeleton. It furthermore highlights the importance and complexity of formin-dependent cytoskeletal regulation in multiple organs and developmental contexts.