Collateral Branches Research Articles

Constructing and Deconstructing the ‘State’: the Case of the Low Countries

The birth of the Low Countries is a thorny issue since the rise of history as an academic discipline in the nineteenth century, and the problem is likely to haunt historians for some time to come. From the eleventh century onwards, the patchwork of principalities that had emerged between France and the German Empire acquired a distinct cachet as most of these principalities became exceptionally urbanized. As Flanders, Brabant, Guelders, Holland, and so on were all fiercely independent, scholars all agree that the increasingly structural socio-economic integration of these urbanised regions did not automatically lead to political integration, even if the ruling dynasties of these principalities were prone to intermarry. Yet, this political integration did take shape in the fifteenth and early sixteenth centuries when a series of contingent factors – ranging from bankrupt princes to accidental deaths – allowed a collateral branch of the royal house of Valois to inherit, to purchase, or to conquer a lengthy string of principalities that eventually stretched from Frisia to the Franche-Comté. This article is part of the discussion forum 'Constructing and Deconstructing the ‘State’: the Case of the Low Countries'.

Breast cancer induced nociceptor aberrant growth and collateral sensory axonal branching.

The tumour and neuron interaction has a significant impact upon disease progression and the patients quality of life. In breast cancer patients, it is known that there is an interaction between the tumour microenvironment and the sensory neurons to influence the progression of cancer as well as pain, though these mechanisms still need to be clearly defined. Here it is demonstrated that in a rodent orthotopic model of breast cancer (MDA MB 231) there was an increase in nerve fibre innervation into the tumour microenvironment (protein gene product 9.5), which were calcitonin gene related peptide positive C fibre nociceptors. In contrast, there was a reduction in myelinated nerve fibres (NF200). A sensory neuronal cell line was cultured in response to conditioned media from MDA MB231 and MCF7 as well as vascular endothelial growth factor-A (VEGF-A). All these experimental conditions induced sensory neuronal growth, with increased formation of collateral axonal branches. Furthermore, it was demonstrated that MDA MB231 and VEGF-A induced sensory neuronal sensitisation in response to capsaicin a TRPV1 agonist. MDA MB231 induced neuronal growth was suppressed by VEGFR2 inhibition (ZM323881 and neutralising antibody DC101), in addition both MDA MB231 and VEGF-A induced neurite growth was attenuated by the inhibition of ARP2/3 complex through co-treatment with CK666. This demonstrates that breast cancer can interact with the sensory nervous system to drive neuritogenesis through a VEGF-A/VEGFR2/ARP2/3 mediated pathway.

A clinical review of early outcomes from contemporary flow modulation versus open, fenestrated and branch technologies in the management of thoracoabdominal aortic aneurysm.

Traditional therapeutic options for complex thoracoabdominal aneurysm include open repair, hybrid repair or endovascular repair (involving fenestrated or branched endografts). The Streamliner Multilayer Flow Modulator has been available for treatment of thoracoabdominal aneurysms since 2010. Its design permits blood flow to perfuse through the mesh in a modus that preserves collateral branch patency, while modulating turbulent to laminar flow within the device. The flow then stagnates over time within the surrounding aneurysm sac. Significant complications, including paraplegia, renal failure and cerebrovascular accident, are much lower with Streamliner Multilayer Flow Modulator treatment. Application of the Streamliner Multilayer Flow Modulator to complex aortic pathologies presents a novel solution to an, as of yet, unmet clinical need, and has resulted in promising clinical outcomes when compared to existing solutions. The Streamliner Multilayer Flow Modulator offers potential for treatment of thoracoabdominal aortic pathologies in patients and is not just confined to those with complexity that dictates no other management options. While current literature illustrates that there is a decreased risk of mortality and associated complications when this new disruptive technology is utilised, there is still a need for prospective, long-term clinical trials, as well as comparative trials to accurately assess outcomes of Streamliner Multilayer Flow Modulator treatment that are both precise and reproducible. This article is a review of current clinical literature regarding contemporary flow modulating technology compared with open, branched and fenestrated managements, presenting early outcomes.

Characterization of the central neural projections to brown, white, and beige adipose tissue.

The functional recruitment of classic brown adipose tissue (BAT) and inducible brown-like or beige fat is, to a large extent, dependent on intact sympathetic neural input. Whereas the central neural circuits directed specifically to BAT or white adipose tissue (WAT) are well established, there is only a developing insight into the nature of neural inputs common to both fat types. Moreover, there is no clear view of the specific central and peripheral innervation of the browned component of WAT: beige fat. The objective of the present study is to examine the neural input to both BAT and WAT in the same animal and, by exposing different cohorts of rats to either thermoneutral or cold conditions, define changes in central neural organization that will ensure that beige fat is appropriately recruited and modulated after browning of inguinal WAT (iWAT). At thermoneutrality, injection of the neurotropic (pseudorabies) viruses into BAT and WAT demonstrates that there are dedicated axonal projections, as well as collateral axonal branches of command neurons projecting to both types of fat. After cold exposure, central neural circuits directed to iWAT showed evidence of reorganization with a greater representation of command neurons projecting to both brown and beiged WAT in hypothalamic (paraventricular nucleus and lateral hypothalamus) and brainstem (raphe pallidus and locus coeruleus) sites. This shift was driven by a greater number of supraspinal neurons projecting to iWAT under cold conditions. These data provide evidence for a reorganization of the nervous system at the level of neural connectivity following browning of WAT.-Wiedmann, N. M., Stefanidis, A., Oldfield, B. J. Characterization of the central neural projections to brown, white, and beige adipose tissue.

Mapping the Role of MAP7 in Axon Collateral Branching.

Neurons have diverse and distinctive dendritic and axonal morphologies. Proper development of these structures is vital for normal function and connectivity. Indeed, abnormal neuronal morphology has been linked to various neurobiological and psychiatric disorders ([Luo and O'Leary, 2005][1]). The

Regulation of axon arborization pattern in the developing chick ciliary ganglion: Possible involvement of caspase 3.

During a certain critical period in the development of the central and peripheral nervous systems, axonal branches and synapses are massively reorganized to form mature connections. In this process, neurons search their appropriate targets, expanding and/or retracting their axons. Recent work suggested that the caspase superfamily regulates the axon morphology. Here, we tested the hypothesis that caspase 3, which is one of the major executioners in apoptotic cell death, is involved in regulating the axon arborization. The embryonic chicken ciliary ganglion was used as a model system of synapse reorganization. A dominant negative mutant of caspase-3 precursor (C3DN) was made and overexpressed in presynaptic neurons in the midbrain to interfere with the intrinsic caspase-3 activity using an in ovo electroporation method. The axon arborization pattern was 3-dimensionally and quantitatively analyzed in the ciliary ganglion. The overexpression of C3DN significantly reduced the number of branching points, the branch order and the complexity index, whereas it significantly elongated the terminal branches at E6. It also increased the internodal distance significantly at E8. But, these effects were negligible at E10 or later. During E6-8, there appeared to be a dynamic balance in the axon arborization pattern between the "targeting" mode, which is accompanied by elongation of terminal branches and the pruning of collateral branches, and the "pathfinding" mode, which is accompanied by the retraction of terminal branches and the sprouting of new collateral branches. The local and transient activation of caspase 3 could direct the balance towards the pathfinding mode.

It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches.

The formation of axon collateral branches from the pre-existing shafts of axons is an important aspect of neurodevelopment and the response of the nervous system to injury. This article provides an overview of the role of the cytoskeleton and signaling mechanisms in the formation of axon collateral branches. Both the actin filament and microtubule components of the cytoskeleton are required for the formation of axon branches. Recent work has begun to shed light on how these two elements of the cytoskeleton are integrated by proteins that functionally or physically link the cytoskeleton. While a number of signaling pathways have been determined as having a role in the formation of axon branches, the complexity of the downstream mechanisms and links to specific signaling pathways remain to be fully determined. The regulation of intra-axonal protein synthesis and organelle function are also emerging as components of signal-induced axon branching. Although much has been learned in the last couple of decades about the mechanistic basis of axon branching we can look forward to continue elucidating this complex biological phenomenon with the aim of understanding how multiple signaling pathways, cytoskeletal regulators and organelles are coordinated locally along the axon to give rise to a branch.

The Effect of Placing Flow-Diverting Stents in Intracranial Collateral Arteries of Miniature Pig.

BackgroundFlow-diverting stent (FDS) has been suggested as an effective intracranial aneurysm treatment. However, the effects of FDS on collateral branches of an aneurysm parent artery still remain unknown. Thus, the present study aimed to comprehensively evaluate the effects of placing a FDS in the intracranial collateral artery, using a miniature pig animal model.Material/MethodsTen healthy miniature pigs were included in the study: one pig was reserved as a control and the remaining nine pigs were placed in three experimental groups: FDS (i.e., Pipeline), LVIS, and Solitaier-AB stent groups. Pigs in the experimental groups were examined by cerebral angiography immediately after stent placement, followed by hemodynamic analyses. In addition, magnetic resonance imaging (MRI) of the brain of pigs in the experimental groups was performed to inspect the brain for obstruction and blood flow. Stents were examined for the growth of neointimas.ResultsThe results showed that neointimas, consisting of smooth muscle cells, collagenous fibers, and macrophages, were 0.67 mm thick on average and partially covered the stent wires. The thickness of neointimas in the FDS group was significantly higher than in the two conventional intracranial stent groups. There was no obvious obstruction identified in collateral arteries where the FDS was placed.ConclusionsThese results indicated that neointimas in collateral arteries of a miniature pig would be slightly thickened after one month of FDS placement; and FDS was shown to be safe for collateral arteries.

Differential roles of α-, β-, and γ-actin in axon growth and collateral branch formation in motoneurons.

Axonal branching and terminal arborization are fundamental events during the establishment of synaptic connectivity. They are triggered by assembly of actin filaments along axon shafts giving rise to filopodia. The specific contribution of the three actin isoforms, Actα, Actβ, and Actγ, to filopodia stability and dynamics during this process is not well understood. Here, we report that Actα, Actβ, and Actγ isoforms are expressed in primary mouse motoneurons and their transcripts are translocated into axons. shRNA-mediated depletion of Actα reduces axonal filopodia dynamics and disturbs collateral branch formation. Knockdown of Actβ reduces dynamic movements of growth cone filopodia and impairs presynaptic differentiation. Ablation of Actβ or Actγ leads to compensatory up-regulation of the two other isoforms, which allows maintenance of total actin levels and preserves F-actin polymerization. Collectively, our data provide evidence for specific roles of different actin isoforms in spatial regulation of actin dynamics and stability in axons of developing motoneurons.

Anatomic features of the oblique branch of lateral circumflex femoral artery and its clinical significance

Objective This study revisits the blood supply of the oblique branches in the light of recent advances in the understanding of the vascular anatomy of the anterolateral thigh, and observes its clinical application effect. Methods From January, 2014 to January, 2016, a prospective intraoperative observational study was performed in 57 consecutive anterolateral thigh flaps, noting the dimensions and locations of the oblique and descending branches and the number and size of the muscle branches supplying the rectus femoris. Twenty-one patients were found with the oblique and descending branches and performed the free flap pedicled with collateral branch of oblique rarus of lateral circumflex femoral artery to fix the foot and ankle in 12 cases. There were 8 males and 4 females with an age range from 23 to 52 years. They were injuried by traffic accident (6 cases), by object hit from height (4 cases),or hurted by machines (2 cases). The locations were foot in 5 cases, ankle in 4 cases, and at the distal shank in 3 cases. The disease duration was 4 hours to 36 hours (mean, 16 hours). Six skin flaps, 4 fascia flap plus skin flap, 2 ramified flaps harvest were then completed as planned. The size of flaps ranged from 7 cm × 11 cm to 8 cm × 21 cm, and the donor sites were closed directly in all cases. Results On the basis of the dimensions and locations of the oblique and descending branches supplying the rectus femoris, all cases were devided into type I (descending branche, 16 cases), type II(the oblique and descending branche, 2 cases), type III(oblique branche, 3 cases). After operation, all the flaps survived, while wound dehiscence accured in 1 case and healed after dressing change and left a slash residual scar without pulling discomfort. The donor site was accompanied by a decrease in the range of peripheral sensory numbness. Early muscle strength of hip and knee arised in 3 cases, got better in 3 months and dispeared in 6 months. By way of telephone follow-up, 12 patients were followed for 3-24 months (mean, 13 months). The appearance and function of the tissue flaps were satisfactory, only linear scar was observed at the donor site, which had less damage and no effect on walking. Conclusion Blood vessels should be carefully identified, while flaps are harvested with diversity of blood supply. As it is improved that the oblique branch of lateral circumflex femoral artery perforator tissue flap is simple and reliable, also can perform various forms of perforator flaps. Key words: Oblique branch, lateral circumflex femoral artery; Perforator flap; Applied anatomy; Repair

Entrapment of the posterior femoral cutaneous nerve and its inferior cluneal branches: anatomical basis of surgery for inferior cluneal neuralgia.

The apparent failure of pudendal nerve surgery in some patients has led us to suggest the possibility of entrapment of other adjacent nerve structures, leading to the concept of inferior cluneal neuralgia. Via its numerous collateral branches, the posterior femoral cutaneous nerve innervates a very extensive territory including the posterior surface of the thigh, the infragluteal fold, the skin over the ischial tuberosity, but also the lateral anal region, scrotum or labium majus via its perineal branch. We described the pathophysiological features of cluneal neuralgia, the surgical technique and our preliminary results. We performed a transmuscular approach leading to the fat of the deep gluteal region. Exploration was continued cranially underneath the piriformis, looking for potential entrapments affecting the posterior femoral cutaneous nerve and the sciatic nerve. Nerve decompression on the lateral surface of the ischial tuberosity was then performed. A constant anatomical finding must be highlighted: the presence of a lateral fibrous expansion from the ischium passing behind the nerves and vessels, especially the posterior femoral cutaneous nerve and its perineal branches. In our patients, release of this expansion allowed decompression of the nerve trapped by this expansion. Cluneal neuralgia constitutes a distinct entity of perineal pain, which must be identified and distinguished from pudendal neuralgia. Surgery should be performed via a transgluteal approach. A lateral ischial obstacle must be investigated, in the form of a constant fibrous expansion, which, like a retinaculum, can cause nerve entrapment.

Cryoinjury-induced acute myocardial infarction model and ameroid constrictor-induced ischemic heart disease model in adult micro-mini pigs for preclinical studies

BackgroundCoronary artery diseases (CAD) are the most commonly occurring disorders in the developed countries. Development of new therapeutics and their success in clinical studies require confirmation of therapeutic effects in large animal models. Swine is an ideal animal model because their anatomical features are similar to humans. However, sometimes their large body size hampers translational research, particularly in cell or tissue transplantation procedures for adult stage and long-term observation studies. We have been developing the smallest experimental pig, called micro-mini pigs (MMPs), for regenerative medicine.MethodsFive- to 14-month-old mature MMPs were used (n = 15, body weight: 13.4 ± 2.14 kg). In the acute myocardial infarction (AMI) model, AMI was induced by cryoinjury (CI). In the ischemic heart disease (IHD) model, IHD was induced using an ameroid constrictor (AC) that was applied to the left anterior descending artery, with the diagonal branches ligated. Cardiac function in both models was assessed by magnetic resonance imaging (MRI) with late gadolinium enhancement, and coronary angiography (CAG) was performed to evaluate the collateral arteries. Animals were sacrificed 4 weeks after procedures to evaluate the pathological changes.ResultsOn MRI, the ejection fraction in CI-induced AMI models decreased from 57.7 ± 3.2% to 35.8 ± 4.7% (Δ62.2%, p = 0.012) (n = 8). In contrast, AC also impaired cardiac function, but some pigs did not develop heart failure due to the development of collateral branches (pre: 54.4 ± 4.4%, post: 41.1 ± 8.0%, Δ75.7%, p = 0.028 [n = 7]). Gadolinium contrast-enhanced MRI and pathological examination confirmed scarring in both models. The proportion of scar area in the left ventricular region of CI-induced AMI models vs. AC-induced IHD models was 19.4% vs. 10.3% (p = 0.046) (MRI) and 17.6% vs. 9.2% (p = 0.046) (pathology). Immunohistological analysis also showed the presence of marked neovascularization in AC models, which led to greater variation in the impairment of cardiac function.ConclusionsMMPs are the smallest available swine for experimental use that are suitable for translational research. They allow for long-term observation of adult pathology. Both models of AMI and IHD were successfully established in MMPs. The MMP preclinical heart failure model may accelerate further development of new treatments for CAD.

MAP7 Regulates Axon Collateral Branch Development in Dorsal Root Ganglion Neurons.

Collateral branches from axons are key components of functional neural circuits that allow neurons to connect with multiple synaptic targets. Like axon growth and guidance, formation of collateral branches depends on the regulation of microtubules, but how such regulation is coordinated to ensure proper circuit development is not known. Based on microarray analysis, we have identified a role for microtubule-associated protein 7 (MAP7) during collateral branch development of dorsal root ganglion (DRG) sensory neurons. We show that MAP7 is expressed at the onset of collateral branch formation. Perturbation of its expression by overexpression or shRNA knockdown alters axon branching in cultured DRG neurons. Localization and time-lapse imaging analysis reveals that MAP7 is enriched at branch points and colocalizes with stable microtubules, but enters the new branch with a delay, suggesting a role in branch maturation. We have also investigated a spontaneous mutant mouse that expresses a truncated MAP7 and found a gain-of-function phenotype both in vitro and in vivo Further domain analysis suggests that the amino half of MAP7 is responsible for branch formation, suggesting a mechanism that is independent of its known interaction with kinesin. Moreover, this mouse exhibits increased pain sensitivity, a phenotype that is consistent with increased collateral branch formation. Therefore, our study not only uncovers the first neuronal function of MAP7, but also demonstrates the importance of proper microtubule regulation in neural circuit development. Furthermore, our data provide new insights into microtubule regulation during axonal morphogenesis and may shed light on MAP7 function in neurological disorders.SIGNIFICANCE STATEMENT Neurons communicate with multiple targets by forming axonal branches. In search of intrinsic factors that control collateral branch development, we identified a role for microtubule-associated protein 7 (MAP7) in dorsal root ganglion sensory neurons. We show that MAP7 expression is developmentally regulated and perturbation of this expression alters branch formation. Cell biological analysis indicates that MAP7 promotes branch maturation. Analysis of a spontaneous mouse mutant suggests a molecular mechanism for branch regulation and the potential influence of collateral branches on pain sensitivity. Our studies thus establish the first neuronal function of MAP7 and demonstrate its role in branch morphogenesis and neural circuit function. These findings may help in our understanding of the contribution of MAP7 to neurological disorders and nerve regeneration.

Drebrin in Neuronal Migration and Axonal Growth.

During development, production of neurons from neural stem cells, migration of neurons from their birthplace to their final location, and extension of neurites, axons, and dendrites are important for the formation of functional neuronal circuits. The actin cytoskeleton has major roles in the morphological development of neurons. In this chapter, we focused on the distribution and function of the actin-binding protein, drebrin, to elucidate the importance of drebrin-bound F-actin in neurons during early developmental stages of neurons in embryonic, postnatal, and adult brains. There are three major isoforms of drebrin in the chicken brain (E1, E2, and A) and two major isoforms in the mammalian brain (E and A). Among these drebrin isoforms, drebrin E1 and E2 in chicken and drebrin E in the mammalian brain are involved in these neuronal stages. In migrating neurons of the developing and adult brain, drebrin is localized at the base of filopodia of leading processes, to regulate neuronal migration. In axonal growth cones, drebrin is localized in the transitional zone to regulate axonal growth by inhibiting actomyosin interactions and mediating the interactions between F-actin and microtubules. For axonal collateral branching, drebrin is localized at axonal actin patches and the base of filopodia, to accelerate the transition from actin patches to filopodia and stabilize the filopodia.

Miguel Ángel Ladero Quesada, Guzmán: La casa ducal de Medina Sidonia en Sevilla y su reino (1282–1521). Madrid: Dykinson, 2015. Paper. Pp. 712; 2 maps and many tables. €35. ISBN: 978-84-9085-274-3.

Miguel Ángel Ladero Quesada, <i>Guzmán: La casa ducal de Medina Sidonia en Sevilla y su reino (1282–1521)</i>. Madrid: Dykinson, 2015. Paper. Pp. 712; 2 maps and many tables. €35. ISBN: 978-84-9085-274-3.

Pseudoaneurysm Endovascular Treatment of a Middle Colic Arterial Branch in a Patient with an Intermittent Digestive Hemorrhage from an Obscure Source: Case Report

Aneurysms of the middle colic arterial branches are extremely rare, the main manifestation occurs due to the rupture and intraabdominal bleeding making death possible in up to 70% of cases. Herein, we report a case of a male patient, who is 50 years old and who displays intermittent, recurrent, and self-limited episodes of a digestive hemorrhage that has been symptomatic during the course of a three-month investigation. After an extensive investigation, the patient was submitted to angiography detecting a pseudoaneurysm in the middle colic branch, being treated with embolization by micro-coils. Intermittent digestive hemorrhages from an obscure source can represent a diagnostic challenge, due to the high degree of clinical suspicion for performing the correct differential diagnosis. Arteriography must not be delayed whenever a pseudoaneurysm with active bleeding is suspected, as this exam is selected for diagnosis and the preferred method for conclusive treatment.

Variability of Ponto-cerebellar Fibers by Diffusion Tensor Imaging in Diverse Brain Malformations.

To describe pontine axonal anomalies across diverse brain malformations. Institutional review board-approved review of magnetic resonance imaging (MRI) and genetic testing of 31 children with brain malformations and abnormal pons by diffusion tensor imaging. Anomalous dorsal pontocerebellar tracts were seen in mid-hindbrain anomalies and in diffuse malformations of cortical development including lissencephaly, gyral disorganization with dysplastic basal ganglia, presumed congenital fibrosis of extraocular muscles type 3, and in callosal agenesis without malformations of cortical development. Heterotopic and hypoplastic corticospinal tracts were seen in callosal agenesis and in focal malformations of cortical development. There were no patterns by chromosomal microarray analysis in the non-lissencephalic brains. In lissencephaly, there was no relationship between severity, deletion size, or appearance of the pontocerebellar tract. Pontine axonal anomalies may relate to defects in precerebellar neuronal migration, chemotactic signaling of the pontine neurons, and/or corticospinal tract pathfinding and collateral branching not detectable with routine genetic testing.

Axonal branching in lateral olfactory tract is promoted by Nogo signaling.

Mitral cells are major projection neurons of the olfactory bulb (OB) that form an axonal bundle known as the lateral olfactory tract (LOT). After axonal bundle formation, collateral branches sprout from primary axons of the LOT. Recently, we identified LOT usher substance (LOTUS) as an endogenous Nogo receptor-1 (NgR1) antagonist and demonstrated that LOTUS contributes to the formation of the LOT axonal bundle. Immunoblots revealed that the expression level of Nogo-A in the OB developmentally increased during axonal collateral formation. Next, we found that the axonal collateral branches were increased in cultured OB neurons from LOTUS-knockout (KO) mice, whereas they were decreased in cultured OB neurons from NgR1-KO mice. Knockdown of Nogo-A in cultured OB neurons reduced the number of axonal collateral branches, suggesting that endogenous Nogo-A induces axonal branching. Finally, the collateral branches of the LOT were increased in LOTUS-KO mice, whereas those in NgR1-KO mice were decreased. Moreover, the abnormal increase of axonal branching observed in LOTUS-KO mice was rescued in the double mutant of LOTUS- and NgR1-KO mice. These findings suggest that Nogo-A and NgR1 interactions may contribute to axonal branching in LOT development.

Transient Developmental Purkinje Cell Axonal Torpedoes in Healthy and Ataxic Mouse Cerebellum.

Information is carried out of the cerebellar cortical microcircuit via action potentials propagated along Purkinje cell axons. In several human neurodegenerative diseases, focal axonal swellings on Purkinje cells – known as torpedoes – have been associated with Purkinje cell loss. Interestingly, torpedoes are also reported to appear transiently during development in rat cerebellum. The function of Purkinje cell axonal torpedoes in health as well as in disease is poorly understood. We investigated the properties of developmental torpedoes in the postnatal mouse cerebellum of wild-type and transgenic mice. We found that Purkinje cell axonal torpedoes transiently appeared on axons of Purkinje neurons, with the largest number of torpedoes observed at postnatal day 11 (P11). This was after peak developmental apoptosis had occurred, when Purkinje cell counts in a lobule were static, suggesting that most developmental torpedoes appear on axons of neurons that persist into adulthood. We found that developmental torpedoes were not associated with a presynaptic GABAergic marker, indicating that they are not synapses. They were seldom found at axonal collateral branch points, and lacked microglia enrichment, suggesting that they are unlikely to be involved in axonal refinement. Interestingly, we found several differences between developmental torpedoes and disease-related torpedoes: developmental torpedoes occurred largely on myelinated axons, and were not associated with changes in basket cell innervation on their parent soma. Disease-related torpedoes are typically reported to contain neurofilament; while the majority of developmental torpedoes did as well, a fraction of smaller developmental torpedoes did not. These differences indicate that developmental torpedoes may not be functionally identical to disease-related torpedoes. To study this further, we used a mouse model of spinocerebellar ataxia type 6 (SCA6), and found elevated disease-related torpedo number at 2 years. However, we found normal levels of developmental torpedoes in these mice. Our findings suggest that the transient emergence of Purkinje cell axonal torpedoes during the second postnatal week in mice represents a normal morphological feature in the developing cerebellar microcircuit.

Transition between synaptic branch formation and synaptogenesis is regulated by the lin-4 microRNA

Axonal branch formation and synaptogenesis are sequential events that are required for the establishment of neuronal connectivity. However, little is known about how the transition between these two events is regulated. Here, we report that the lin-4 microRNA can regulate the transition between branch formation and synaptogenesis in the PLM axon of C. elegans. The PLM axon grows a collateral branch during the early L1 stage and undergoes synaptogenesis during the late L1 stage. Loss of the lin-4 microRNA disrupts synaptogenesis during the late L1 stage, suggesting that lin-4 promotes synaptogenesis. Conversely, the target of lin-4, the LIN-14 transcription factor, promotes PLM branch formation and inhibits synaptogenesis during the early L1 stage. Moreover, we present genetic evidence suggesting that synaptic vesicle transport is required for PLM branch formation and that the role of LIN-14 is to promote transport of synaptic vesicles to the region of future branch growth. These observations provide a novel mechanism whereby lin-4 promotes the transition from branch formation to synaptogenesis by repressing the branch-promoting and synaptogenesis-inhibiting activities of LIN-14.