@article{Hosseini2025,

title = {AutoGaitA: A versatile quantitative framework for kinematic analyses across species, perturbations and behaviours},

author = {Mahan Hosseini and Ines Klein and Veronika Wunderle and Carolin Semmler and Taylan D. Kuzu and Ann-Kathrin Kramer and Marianna Tolve and Vlad Mardare and Ana Galvao and Moritz Haustein and Christian Grefkes and Tatiana Korotkova and Ansgar Büschges and Gereon R. Fink and Peter H. Weiss and Silvia Daun and Graziana Gatto},

url = {https://www.biorxiv.org/content/10.1101/2024.04.14.589409v2 https://www.biorxiv.org/content/10.1101/2024.04.14.589409v2.abstract},

doi = {10.1101/2024.04.14.589409},

issn = {2692-8205},

year  = {2025},

date = {2025-08-01},

journal = {bioRxiv},

pages = {2024.04.14.589409},

publisher = {Cold Spring Harbor Laboratory},

institution = {bioRxiv},

abstract = {Individual behaviours require the nervous system to execute specialised motor programs, each characterised by unique patterns of coordinated movements across body parts. Deep learning approaches for body-posture tracking have facilitated the analysis of such motor programs. However, translating the resulting time-stamped coordinate datasets into meaningful kinematic representations of motor programs remains a long-standing challenge. We developed the versatile quantitative framework AutoGaitA (Automated Gait Analysis), a Python toolbox that enables comparisons of motor programs at multiple levels of granularity and across tracking methods, species and behaviours. AutoGaitA allowed us to demonstrate that flies, mice, and humans, despite divergent biomechanics, converge on the age-dependent loss of propulsive strength, and that, in mice, locomotor programs adapt as an integrated function of both age and task difficulty. AutoGaitA represents a truly universal framework for robust analyses of motor programs and changes thereof in health and disease, and across species and behaviours. ### Competing Interest Statement The authors have declared no competing interest. Deutsche Forschungsgemeinschaft, SFB 1451 Project-ID 431549029-INF, 431549029-Z02, 328 431549029-Z03},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Yao2025,

title = {The spinal premotor network driving scratching flexor and extensor alternation},

author = {Mingchen Yao and Akira Nagamori and Sandrina Campos Maçãs and Eiman Azim and Tatyana Sharpee and Martyn Goulding and David Golomb and Graziana Gatto},

url = {https://www.cell.com/action/showFullText?pii=S2211124725006163 https://www.cell.com/action/showAbstract?pii=S2211124725006163 https://www.cell.com/cell-reports/abstract/S2211-1247(25)00616-3},

doi = {10.1016/j.celrep.2025.115845},

issn = {22111247},

year  = {2025},

date = {2025-06-01},

journal = {Cell Reports},

volume = {44},

number = {6},

publisher = {Elsevier B.V.},

abstract = {Rhythmic motor behaviors are generated by neural networks termed central pattern generators (CPGs). Although locomotor CPGs have been extensively characterized, it remains unknown how the neuronal populations composing them interact to generate adaptive rhythms in mammals. We explored the cooperation dynamics among the three main populations of ipsilaterally projecting spinal CPG neurons—V1, V2a, and V2b neurons—in scratch reflex rhythmogenesis. Individual ablation of the three neuronal populations reduced the oscillation frequency. Activation of excitatory V2a neurons enhanced the oscillation frequency, while activating inhibitory V1 neurons suppressed movement. Building on these findings, we developed a neuromechanical model made of self-oscillating flexor and extensor modules coupled via inhibition. Rhythm frequency is increased by strong intra-module inhibition and facilitation mechanisms in excitatory neurons and decreased by strong inter-module inhibition. In sum, we describe how genetically identified neuron types and the strengths of their synaptic connections drive scratch rhythmogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tolve2025,

title = {The endocytic adaptor AP-2 maintains Purkinje cell function by balancing cerebellar parallel and climbing fiber synapses},

author = {Marianna Tolve and Janine Tutas and Ebru Özer-Yildiz and Ines Klein and Anne Petzold and Veronika J. Fritz and Melina Overhoff and Quinn Silverman and Ellie Koletsou and Filip Liebsch and Guenter Schwarz and Tatiana Korotkova and Silvana Valtcheva and Graziana Gatto and Natalia L. Kononenko},

url = {https://www.biorxiv.org/content/10.1101/2024.06.02.596459v2 https://www.biorxiv.org/content/10.1101/2024.06.02.596459v2.abstract},

doi = {10.1016/j.celrep.2025.115256},

issn = {22111247},

year  = {2025},

date = {2025-06-01},

journal = {Cell Reports},

volume = {44},

number = {2},

pages = {2024.06.02.596459},

publisher = {Cold Spring Harbor Laboratory},

institution = {bioRxiv},

abstract = {The loss of cerebellar Purkinje cells is a hallmark of neurodegenerative movement disorders, but the mechanisms remain enigmatic. We show that endocytic adaptor protein complex 2 (AP-2) is crucial for Purkinje cell survival. Using mouse genetics, viral tracing, calcium imaging, and kinematic analysis, we demonstrate that loss of the AP-2 μ subunit in Purkinje cells leads to early-onset ataxia and progressive degeneration. Synaptic dysfunction, marked by an overrepresentation of parallel fibers (PFs) over climbing fibers (CFs), precedes Purkinje cell loss. Mechanistically, AP-2 interacts with the PF-enriched protein GRID2IP, and its loss triggers GRID2IP degradation and glutamate δ2 receptor (GLURδ2) accumulation, leading to an excess of PFs while CFs are reduced. The overrepresentation of PFs increases Purkinje cell network activity, which is mitigated by enhancing glutamate clearance with ceftriaxone. These findings highlight the role of AP-2 in regulating GRID2IP levels in Purkinje cells to maintain PF-CF synaptic balance and prevent motor dysfunction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tutas2025,

title = {Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity},

author = {Janine Tutas and Marianna Tolve and Ebru Özer-Yildiz and Lotte Ickert and Ines Klein and Quinn Silverman and Filip Liebsch and Frederik Dethloff and Patrick Giavalisco and Heike Endepols and Theodoros Georgomanolis and Bernd Neumaier and Alexander Drzezga and Guenter Schwarz and Bernard Thorens and Graziana Gatto and Christian Frezza and Natalia L. Kononenko},

url = {https://www.nature.com/articles/s42255-024-01196-4},

doi = {10.1038/s42255-024-01196-4},

issn = {2522-5812},

year  = {2025},

date = {2025-01-01},

journal = {Nature Metabolism 2025},

pages = {1–24},

publisher = {Nature Publishing Group},

abstract = {Dysfunctions in autophagy, a cellular mechanism for breaking down components within lysosomes, often lead to neurodegeneration. The specific mechanisms underlying neuronal vulnerability due to autophagy dysfunction remain elusive. Here we show that autophagy contributes to cerebellar Purkinje cell (PC) survival by safeguarding their glycolytic activity. Outside the conventional housekeeping role, autophagy is also involved in the ATG5-mediated regulation of glucose transporter 2 (GLUT2) levels during cerebellar maturation. Autophagy-deficient PCs exhibit GLUT2 accumulation on the plasma membrane, along with increased glucose uptake and alterations in glycolysis. We identify lysophosphatidic acid and serine as glycolytic intermediates that trigger PC death and demonstrate that the deletion of GLUT2 in ATG5-deficient mice mitigates PC neurodegeneration and rescues their ataxic gait. Taken together, this work reveals a mechanism for regulating GLUT2 levels in neurons and provides insights into the neuroprotective role of autophagy by controlling glucose homeostasis in the brain. Tutas et al. show an unconventional role for autophagy in the regulation of glycolytic flux in cerebellar Purkinje cells by maintaining the levels of the glucose transporter GLUT2.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Trevisan2024,

title = {The transcriptomic landscape of spinal V1 interneurons reveals a role for En1 in specific elements of motor output},

author = {Alexandra J. Trevisan and Katie Han and Phillip Chapman and Anand S. Kulkarni and Jennifer M. Hinton and Cody Ramirez and Ines Klein and Graziana Gatto and Mariano I. Gabitto and Vilas Menon and Jay B. Bikoff},

url = {https://www.biorxiv.org/content/10.1101/2024.09.18.613279v1 https://www.biorxiv.org/content/10.1101/2024.09.18.613279v1.abstract},

doi = {10.1101/2024.09.18.613279},

year  = {2024},

date = {2024-09-01},

journal = {bioRxiv},

pages = {2024.09.18.613279},

publisher = {Cold Spring Harbor Laboratory},

institution = {bioRxiv},

abstract = {Neural circuits in the spinal cord are composed of diverse sets of interneurons that play crucial roles in shaping motor output. Despite progress in revealing the cellular architecture of the spinal cord, the extent of cell type heterogeneity within interneuron populations remains unclear. Here, we present a single-nucleus transcriptomic atlas of spinal V1 interneurons across postnatal development. We find that the core molecular taxonomy distinguishing neonatal V1 interneurons perdures into adulthood, suggesting conservation of function across development. Moreover, we identify a key role for En1, a transcription factor that marks the V1 population, in specifying one unique subset of V1Pou6f2 interneurons. Loss of En1 selectively disrupts the frequency of rhythmic locomotor output but does not disrupt flexion/extension limb movement. Beyond serving as a molecular resource for this neuronal population, our study highlights how deep neuronal profiling provides an entry point for functional studies of specialized cell types in motor output. ### Competing Interest Statement The authors have declared no competing interest.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chung2023,

title = {Myomatrix arrays for high-definition muscle recording},

author = {Bryce Chung and Muneeb Zia and Kyle A Thomas and Jonathan A Michaels and Amanda Jacob and Andrea Pack and Matthew J Williams and Kailash Nagapudi and Lay Heng Teng and Eduardo Arrambide and Logan Ouellette and Nicole Oey and Rhuna Gibbs and Philip Anschutz and Jiaao Lu and Yu Wu and Mehrdad Kashefi and Tomomichi Oya and Rhonda Kersten and Alice C Mosberger and Sean O'Connell and Runming Wang and Hugo Marques and Ana Rita Mendes and Constanze Lenschow and Gayathri Kondakath and Jeong Jun Kim and William Olson and Kiara N Quinn and Pierce Perkins and Graziana Gatto and Ayesha Thanawalla and Susan Coltman and Taegyo Kim and Trevor Smith and Ben Binder-Markey and Martin Zaback and Christopher K Thompson and Simon Giszter and Abigail Person and Martyn Goulding and Eiman Azim and Nitish Thakor and Daniel O'Connor and Barry Trimmer and Susana Q Lima and Megan R Carey and Chethan Pandarinath and Rui M Costa and J Andrew Pruszynski and Muhannad Bakir and Samuel J Sober},

url = {https://www.biorxiv.org/content/10.1101/2023.02.21.529200v1 https://www.biorxiv.org/content/10.1101/2023.02.21.529200v1.abstract},

doi = {10.7554/elife.88551.3},

year  = {2023},

date = {2023-02-01},

journal = {eLife},

volume = {12},

pages = {2023.02.21.529200},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous system's actual motor output – the activation of muscle fibers by motor neurons – typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices (‘Myomatrix arrays') that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a ‘motor unit,' during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous system's motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and identifying pathologies of the motor system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hayashi2023,

title = {A spinal synergy of excitatory and inhibitory neurons coordinates ipsilateral body movements},

author = {Marito Hayashi and Miriam Gullo and Gokhan Senturk and Stefania Di Costanzo and Shinji C. Nagasaki and Ryoichiro Kageyama and Itaru Imayoshi and Martyn Goulding and Samuel L. Pfaff and Graziana Gatto},

url = {https://elifesciences.org/reviewed-preprints/89362},

doi = {10.7554/ELIFE.89362},

year  = {2023},

date = {2023-01-01},

journal = {eLife},

volume = {12},

publisher = {eLife Sciences Publications Limited},

abstract = {Innate and goal-directed movements require a high-degree of trunk and appendicular muscle coordination to preserve body stability while ensuring the correct execution of the motor action. The spinal neural circuits underlying motor execution and postural stability are finely modulated by propriospinal, sensory and descending feedback, yet how distinct spinal neuron populations cooperate to control body stability and limb coordination remains unclear. Here, we identified a spinal microcircuit composed of V2 lineage-derived excitatory (V2a) and inhibitory (V2b) neurons that together coordinate ipsilateral body movements during locomotion. Inactivation of the entire V2 neuron lineage does not impair intralimb coordination but destabilizes body balance and ipsilateral limb coupling, causing mice to adopt a compensatory festinating gait and be unable to execute skilled locomotor tasks. Taken together our data suggest that during locomotion the excitatory V2a and inhibitory V2b neurons act antagonistically to control intralimb coordination, and synergistically to coordinate forelimb and hindlimb movements. Thus, we suggest a new circuit architecture, by which neurons with distinct neurotransmitter identities employ a dual-mode of operation, exerting either synergistic or opposing functions to control different facets of the same motor behavior.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Peirs2021,

title = {Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury},

author = {Cedric Peirs and Sean Paul G. Williams and Xinyi Zhao and Cynthia M Arokiaraj and David W Ferreira and Myung Noh and Kelly M Smith and Priyabrata Halder and Kelly A Corrigan and Jeremy Y Gedeon and Suh Jin Lee and Graziana Gatto and David Chi and Sarah E Ross and Martyn Goulding and Rebecca P Seal},

url = {http://www.ncbi.nlm.nih.gov/pubmed/33181066},

doi = {10.1016/j.neuron.2020.10.027},

issn = {10974199},

year  = {2021},

date = {2021-11-01},

journal = {Neuron},

volume = {109},

number = {1},

pages = {73–90.e7},

publisher = {Elsevier},

abstract = {The spinal dorsal horn is a major site for the induction and maintenance of mechanical allodynia, but the circuitry that underlies this clinically important form of pain remains unclear. The studies presented here provide strong evidence that the neural circuits conveying mechanical allodynia in the dorsal horn differ by the nature of the injury. Calretinin (CR) neurons in lamina II inner convey mechanical allodynia induced by inflammatory injuries, while protein kinase C gamma (PKCγ) neurons at the lamina II/III border convey mechanical allodynia induced by neuropathic injuries. Cholecystokinin (CCK) neurons located deeper within the dorsal horn (laminae III–IV) are important for both types of injuries. Interestingly, the Maf+ subset of CCK neurons is composed of transient vesicular glutamate transporter 3 (tVGLUT3) neurons, which convey primarily dynamic allodynia. Identification of an etiology-based circuitry for mechanical allodynia in the dorsal horn has important implications for the mechanistic and clinical understanding of this condition.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gatto2020,

title = {A Functional Topographic Map for Spinal Sensorimotor Reflexes},

author = {Graziana Gatto and Steeve Bourane and Xiangyu Ren and Stefania Di Costanzo and Peter K. Fenton and Priyabrata Halder and Rebecca P. Seal and Martyn D. Goulding},

url = {https://linkinghub.elsevier.com/retrieve/pii/S0896627320307716},

doi = {10.1016/j.neuron.2020.10.003},

issn = {10974199},

year  = {2021},

date = {2021-11-01},

journal = {Neuron},

volume = {109},

number = {1},

pages = {91–104.e5},

publisher = {Elsevier},

abstract = {Cutaneous somatosensory modalities play pivotal roles in generating a wide range of sensorimotor behaviors, including protective and corrective reflexes that dynamically adapt ongoing movement and posture. How interneurons (INs) in the dorsal horn encode these modalities and transform them into stimulus-appropriate motor behaviors is not known. Here, we use an intersectional genetic approach to functionally assess the contribution that eight classes of dorsal excitatory INs make to sensorimotor reflex responses. We demonstrate that the dorsal horn is organized into spatially restricted excitatory modules composed of molecularly heterogeneous cell types. Laminae I/II INs drive chemical itch-induced scratching, laminae II/III INs generate paw withdrawal movements, and laminae III/IV INs modulate dynamic corrective reflexes. These data reveal a key principle in spinal somatosensory processing, namely, sensorimotor reflexes are driven by the differential spatial recruitment of excitatory neurons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gatto2019,

title = {Neuronal diversity in the somatosensory system: bridging the gap between cell type and function},

author = {Graziana Gatto and Kelly Megan Smith and Sarah Elizabeth Ross and Martyn Goulding},

url = {http://www.ncbi.nlm.nih.gov/pubmed/30953870 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6583900},

doi = {10.1016/j.conb.2019.03.002},

issn = {18736882},

year  = {2019},

date = {2019-06-01},

journal = {Current Opinion in Neurobiology},

volume = {56},

pages = {167–174},

publisher = {Elsevier Ltd},

abstract = {A recent flurry of genetic studies in mice have provided key insights into how the somatosensory system is organized at a cellular level to encode itch, pain, temperature, and touch. These studies are largely predicated on the idea that functional cell types can be identified by their unique developmental provenance and gene expression profile. However, the extent to which gene expression profiles can be correlated with functional cell types and circuit organization remains an open question. In this review, we focus on recent progress in characterizing the sensory afferent and dorsal horn neuron cell types that process cutaneous somatosensory information and ongoing circuit studies that are beginning to bridge the divide between cell type and function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gatto2018,

title = {Locomotion Control: Brainstem Circuits Satisfy the Need for Speed},

author = {Graziana Gatto and Martyn Goulding},

doi = {10.1016/j.cub.2018.01.068},

issn = {09609822},

year  = {2018},

date = {2018-01-01},

journal = {Current Biology},

volume = {28},

number = {6},

abstract = {Three new and closely complementary studies have defined the architecture of the circuits underlying the descending control of locomotion, identifying neurons that drive fast motor responses and those that seem to be specialised for exploratory behaviors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Koch2017,

title = {RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait},

author = {Stephanie C. Koch and Marta Garcia Del Barrio and Antoine Dalet and Graziana Gatto and Thomas Günther and Jingming Zhang and Barbara Seidler and Dieter Saur and Roland Schüle and Martyn Goulding},

url = {https://linkinghub.elsevier.com/retrieve/pii/S0896627317310644},

doi = {10.1016/j.neuron.2017.11.011},

issn = {10974199},

year  = {2017},

date = {2017-12-01},

journal = {Neuron},

volume = {96},

number = {6},

pages = {1419–1431.e5},

abstract = {Animals depend on sensory feedback from mechanosensory afferents for the dynamic control of movement. This sensory feedback needs to be selectively modulated in a task- and context-dependent manner. Here, we show that inhibitory interneurons (INs) expressing the RORβ orphan nuclear receptor gate sensory feedback to the spinal motor system during walking and are required for the production of a fluid locomotor rhythm. Genetic manipulations that abrogate inhibitory RORβ IN function result in an ataxic gait characterized by exaggerated flexion movements and marked alterations to the step cycle. Inactivation of RORβ in inhibitory neurons leads to reduced presynaptic inhibition and changes to sensory-evoked reflexes, arguing that the RORβ inhibitory INs function to suppress the sensory transmission pathways that activate flexor motor reflexes and interfere with the ongoing locomotor program. Video Abstract [Figure presented] Koch et al. identify an inhibitory spinal circuit that is required for fluid rhythmic stepping movements. Inhibitory RORβ+ neurons in the spinal cord selectively gate proprioceptive transmission during locomotion by a presynaptic mechanism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gatto2014,

title = {EphA4 receptor shedding regulates spinal motor axon guidance},

author = {Graziana Gatto and Daniel Morales and Artur Kania and Rüdiger Klein},

doi = {10.1016/j.cub.2014.08.028},

issn = {09609822},

year  = {2014},

date = {2014-01-01},

journal = {Current Biology},

volume = {24},

number = {20},

pages = {2355–2365},

abstract = {Background: Proteolytic processing of axon guidance receptors modulates their expression and functions. Contact repulsion by membrane-associated ephrins and Eph receptors was proposed to be facilitated by ectodomain cleavage, but whether this phenomenon is required for axon guidance in vivo is unknown. Results: In support of established models, we find that cleavage of EphA4 promotes cell-cell and growth cone-cell detachment in vitro. Unexpectedly, however, a cleavage resistant isoform of EphA4 is as effective as a wild-type EphA4 in redirecting motor axons in limbs. Mice in which EphA4 cleavage is genetically abolished have motor axon guidance defects, suggesting an important role of EphA4 cleavage in nonneuronal tissues such as the limb mesenchyme target of spinal motor neurons. Indeed, we find that blocking EphA4 cleavage increases expression of full-length EphA4 in limb mesenchyme, which - via cis-attenuation - apparently reduces the effective concentration of ephrinAs capable of triggering EphA4 forward signaling in the motor axons. Conclusions: We propose that EphA4 cleavage is required to establish the concentration differential of active ephrins in the target tissue that is required for proper axon guidance. Our study reveals a novel mechanism to regulate guidance decision at an intermediate target based on the modulation of ligand availability by the proteolytic processing of the receptor. © 2014 Elsevier Ltd. All rights reserved..},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gatto2013,

title = {Protein Tyrosine Phosphatase Receptor Type O Inhibits Trigeminal Axon Growth and Branching by Repressing TrkB and Ret Signaling.},

author = {Graziana Gatto and Irina Dudanova and Philipp Suetterlin and Alun M Davies and Uwe Drescher and John L Bixby and Rüdiger Klein},

url = {http://www.ncbi.nlm.nih.gov/pubmed/23516305},

doi = {10.1523/JNEUROSCI.4707-12.2013},

issn = {1529-2401},

year  = {2013},

date = {2013-03-01},

journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},

volume = {33},

number = {12},

pages = {5399–410},

abstract = {Axonal branches of the trigeminal ganglion (TG) display characteristic growth and arborization patterns during development. Subsets of TG neurons express different receptors for growth factors, but these are unlikely to explain the unique patterns of axonal arborizations. Intrinsic modulators may restrict or enhance cellular responses to specific ligands and thereby contribute to the development of axon growth patterns. Protein tyrosine phosphatase receptor type O (PTPRO), which is required for Eph receptor-dependent retinotectal development in chick and for development of subsets of trunk sensory neurons in mouse, may be such an intrinsic modulator of TG neuron development. PTPRO is expressed mainly in TrkB-expressing (TrkB(+)) and Ret(+) mechanoreceptors within the TG during embryogenesis. In PTPRO mutant mice, subsets of TG neurons grow longer and more elaborate axonal branches. Cultured PTPRO(-/-) TG neurons display enhanced axonal outgrowth and branching in response to BDNF and GDNF compared with control neurons, indicating that PTPRO negatively controls the activity of BDNF/TrkB and GDNF/Ret signaling. Mouse PTPRO fails to regulate Eph signaling in retinocollicular development and in hindlimb motor axon guidance, suggesting that chick and mouse PTPRO have different substrate specificities. PTPRO has evolved to fine tune growth factor signaling in a cell-type-specific manner and to thereby increase the diversity of signaling output of a limited number of receptor tyrosine kinases to control the branch morphology of developing sensory neurons. The regulation of Eph receptor-mediated developmental processes by protein tyrosine phosphatases has diverged between chick and mouse.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dudanova2010,

title = {GDNF acts as a chemoattractant to support ephrinA-induced repulsion of limb motor axons.},

author = {Irina Dudanova and Graziana Gatto and Rüdiger Klein},

url = {http://www.ncbi.nlm.nih.gov/pubmed/21109439},

doi = {10.1016/j.cub.2010.11.021},

issn = {1879-0445},

year  = {2010},

date = {2010-12-01},

journal = {Current biology : CB},

volume = {20},

number = {23},

pages = {2150–6},

abstract = {Despite the abundance of guidance cues in vertebrate nervous systems, little is known about cooperation between them. Motor axons of the lateral motor column (LMC(L)) require two ligand/receptor systems, ephrinA/EphA4 and glial cell line-derived neurotrophic factor (GDNF)/Ret, to project to the dorsal limb. Deletion of either EphA4 or Ret in mice leads to rerouting of a portion of LMC(L) axons to the ventral limb, a phenotype enhanced in EphA4;Ret double mutants. The guidance errors in EphA4 knockouts were attributed to the lack of repulsion from ephrinAs in the ventral mesenchyme. However, it has remained unclear how GDNF, expressed dorsally next to the choice point, acts on motor axons and cooperates with ephrinAs. Here we show that GDNF induces attractive turning of LMC(L) axons. When presented in countergradients, GDNF and ephrinAs cooperate in axon turning, indicating that the receptors Ret and EphA4 invoke opposite effects within the same growth cone. GDNF also acts in a permissive manner by reducing ephrinA-induced collapse and keeping the axons in a growth-competent state. This is the first example of two opposing cues promoting the same trajectory choice at an intermediate target.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}