BMP7 promotes cardiomyocyte regeneration in zebrafish and adult mice.

Zebrafish have a lifelong cardiac regenerative ability after damage, whereas mammals lose this capacity during early postnatal development. This study investigated whether the declining expression of growth factors during postnatal mammalian development contributes to the decrease of cardiomyocyte regenerative potential. Besides confirming the proliferative ability of neuregulin 1 (NRG1), interleukin (IL)1b, receptor activator of nuclear factor kappa-Β ligand (RANKL), insulin growth factor (IGF)2, and IL6, we identified other potential pro-regenerative factors, with BMP7 exhibiting the most pronounced efficacy. Bmp7 knockdown in neonatal mouse cardiomyocytes and loss-of-function in adult zebrafish during cardiac regeneration reduced cardiomyocyte proliferation, indicating that Bmp7 is crucial in the regenerative stages of mouse and zebrafish hearts. Conversely, bmp7 overexpression in regenerating zebrafish or administration at post-mitotic juvenile and adult mouse stages, in vitro and in vivo following myocardial infarction, enhanced cardiomyocyte cycling. Mechanistically, BMP7 stimulated proliferation through BMPR1A/ACVR1 and ACVR2A/BMPR2 receptors and downstream SMAD5, ERK, and AKT signaling. Overall, BMP7 administration is a promising strategy for heart regeneration.

The chemicals between us-First results of the cluster analyses on anatomy embalming procedures in the German-speaking countries.

Hands-on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German-speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German-speaking Europe. Clusters were established for "ethanol"-, formaldehyde-based ("FA"), and "other" embalming procedures, depending on the chemicals considered the most relevant for each protocol. The logistical framework, volumes of chemicals, and infrastructure were found to be highly diverse between the groups and protocols. Formaldehyde quantities deployed per annum were three-fold higher in the "FA" (223 L/a) compared to the "ethanol" (71.0 L/a) group, but not for "other" (97.8 L/a), though the volumes injected per body were similar. "FA" was strongly related to table-borne air ventilation and total fixative volumes ≤1000 L. "Ethanol" was strongly related to total fixative volumes >1000 L, ceiling- and floor-borne air ventilation, and explosion-proof facilities. Air ventilation was found to be installed symmetrically in the mortuary and dissection facilities. Certain predictors exist for the interplay between the embalming used in a given infrastructure and technical measures. The here-established cluster analysis may serve as decision supportive tool when considering altering embalming protocols or establishing joint protocols between institutions, following a best practice approach to cater toward best-suited tissue characteristics for educational purposes, while simultaneously addressing future demands on exposure limits.

Holoprosencephaly with a Special Form of Anophthalmia Result from Experimental Induction of bmp4, Oversaturating BMP Antagonists in Zebrafish.

Vision is likely our most prominent sense and a correct development of the eye is at its basis. Early eye development is tightly connected to the development of the forebrain. A single eye field and the prospective telencephalon are situated within the anterior neural plate (ANP). During normal development, both domains are split and consecutively, two optic vesicles and two telencephalic lobes emerge. If this process is hampered, the domains remain condensed at the midline. The resulting developmental disorder is termed holoprosencephaly (HPE). The typical ocular finding associated with intense forms of HPE is cyclopia. However, also anophthalmia and coloboma can be associated with HPE. Here, we report that a correct balance of Bone morphogenetic proteins (BMPs) and their antagonists are important for forebrain and eye field cleavage. Experimental induction of a BMP ligand results in a severe form of HPE showing anophthalmia. We identified a dysmorphic forebrain containing retinal progenitors, which we termed crypt-oculoid. Optic vesicle evagination is impaired due to a loss of rx3 and, consecutively, of cxcr4a. Our data further suggest that the subduction of prospective hypothalamic cells during neurulation and neural keel formation is affected by the induction of a BMP ligand.

Regulation of electrogenic Na+ /HCO3- cotransporter 1 (NBCe1) function and its dependence on m-TOR mediated phosphorylation of Ser245.

Astrocytes are pivotal responders to alterations of extracellular pH, primarily by regulation of their principal acid-base transporter, the membrane-bound electrogenic Na+ /bicarbonate cotransporter 1 (NBCe1). Here, we describe amammalian target of rapamycin (mTOR)-dependent and NBCe1-mediated astroglial response to extracellular acidosis. Using primary mouse cortical astrocytes, we investigated the effect of long-term extracellular metabolic acidosis on regulation of NBCe1 and elucidated the underlying molecular mechanisms by immunoblotting, biotinylation of surface proteins, intracellular H+ recording using the H+ -sensitive dye 2',7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein, and phosphoproteomic analysis. The results showed significant increase of NBCe1-mediated recovery of intracellular pH from acidification in WT astrocytes, but not in cortical astrocytes from NBCe1-deficient mice. Acidosis-induced upregulation of NBCe1 activity was prevented following inhibition of mTOR signaling by rapamycin. Yet, during acidosis or following exposure of astrocytes to rapamycin, surface protein abundance of NBCe1 remained -unchanged. Mutational analysis in HeLa cells suggested that NBCe1 activity was dependent on phosphorylation state of Ser245 , a residue conserved in all NBCe1 variants. Moreover, phosphorylation state of Ser245 is regulated by mTOR and is inversely correlated with NBCe1 transport activity. Our results identify pSer245 as a novel regulator of NBCe1 functional expression. We propose that context-dependent and mTOR-mediated multisite phosphorylation of serine residues of NBCe1 is likely to be a potent mechanism contributing to the response of astrocytes to acid/base challenges during pathophysiological conditions.

Interprofessional education in medical and physiotherapy studies for future collaboration.

BACKGROUND: Interprofessional education (IPE) for medical and healthcare professions is highly relevant. It increases knowledge and skills, but also helps to foster the development of collaboration, which is essential for optimal patient care. One important aspect of IPE is to better understand profession's individual attitudes and perceptions towards interprofessionalism and the expected roles and skills for future collaboration in the context of patient care. METHODS: We offered IPE workshops using a peer assisted learning approach, with the focus on anatomy in the area of the lower back and hip. The workshops were attended by medical and physiotherapy students and consisted of three consecutive training sessions with the topics anatomical prosections, anatomy in vivo and orthopedics testing. We focused on student's attitudes and perceptions regarding the relevance of IPE and their expected skills in interprofessionalism. An established questionnaire was used as an instrument for self-assessment before and after the interprofessional experience. To evaluate for significance, analysis was carried out for all groups on pre- and post-course item mean differences. RESULTS: Pre-post score comparison for all groups combined demonstrated significant increase in terms of perceptions and attitudes for several items related to interprofessionalism and interprofessional skills. Medical and physiotherapy students rated themselves significantly higher for different questionnaire items. Students, who had obtained a professional qualification prior to their current studies, rated themselves significantly higher on certain items compared to those who had not. CONCLUSIONS: The results from this brief interprofessional anatomy experience are encouraging. The course led to meaningful improvements in competencies that are highly relevant for effective interprofessional collaboration in the future. Furthermore, identification of differences in professional group perceptions can be useful for development of future IPE workshops.

BMP Signaling Interferes with Optic Chiasm Formation and Retinal Ganglion Cell Pathfinding in Zebrafish.

Decussation of axonal tracts is an important hallmark of vertebrate neuroanatomy resulting in one brain hemisphere controlling the contralateral side of the body and also computing the sensory information originating from that respective side. Here, we show that BMP interferes with optic chiasm formation and RGC pathfinding in zebrafish. Experimental induction of BMP4 at 15 hpf results in a complete ipsilateral projection of RGC axons and failure of commissural connections of the forebrain, in part as the result of an interaction with shh signaling, transcriptional regulation of midline guidance cues and an affected optic stalk morphogenesis. Experimental induction of BMP4 at 24 hpf, resulting in only a mild repression of forebrain shh ligand expression but in a broad expression of pax2a in the diencephalon, does not per se prevent RGC axons from crossing the midline. It nevertheless shows severe pathologies of RGC projections e.g., the fasciculation of RGC axons with the ipsilateral optic tract resulting in the innervation of one tectum by two eyes or the projection of RGC axons in the direction of the contralateral eye.

An interprofessional teaching approach for medical and physical therapy students to learn functional anatomy and clinical examination of the lower spine and hip.

INTRODUCTION: Pain of the lower back is a frequent symptom and is treated by different health professions. Anatomical as well as clinical knowledge is utmost important for all professions involved in this field. Here, we present a model that brings together an interprofessional team of experts to teach functional and clinical anatomy of the lower spine and hip area to medical and physical therapy students. METHODS: Two groups of medical students (n=60) and physical therapy students (n=77) were designated to two interprofessional clusters, with each cluster of students participating in three workshops, each lasting 40min. Workshops were guided by university anatomists, an orthopedic physician and physical therapists, and each provided specialized training, such as the conduction of clinical, orthopedic functional tests, the identification and palpation of anatomical structures and demonstrations of human anatomical joint prosections. A questionnaire, consisting of 18 questions regarding subjective anatomical and clinical knowledge and application of clinical assessment techniques was used as the evaluation tool before and after participation in the course. Furthermore, the amount of knowledge gained from peer group participants from the other profession versus the knowledge gained from the instructors was assessed. Descriptive statistics of data as well as quantitative data analysis was carried out for pre-post analysis. RESULTS: A total of 148 students participated in the pre-course evaluation and self-assessment and 113 students completed the post-course evaluation and self-assessment. 11 of the students, who completed the pre-course evaluation, and five students who completed the post-course evaluation failed to reveal their affiliation and these were only included in the general and corresponding cluster analysis. A final 132 pre-questionnaire and 97 post-questionnaire results were included in the analyses due to a likely group response bias. Scores for all combined groups showed an increase in the pre-post evaluation of 11.7% (P<.001). Cluster 1 and 2 (pre-post) score comparisons showed an increase of 13.7% (P<.001) and 8.8% (P<.001) respectively. A subgroup pre-post-questionnaire analysis demonstrated that medical students from both clusters had the highest increase in scores (17.6% and 19.9%) in comparison to their physical therapy counterparts (9.1% and 5.8%) (P<.001). Specifically, medical students profited highly from the anatomy in vivo (palpation) as well as clinical, orthopedic assessment exercises. Sub-question analyses showed that students learned from each other as well as from an interprofessional team of guiding experts/instructors, though mostly from the latter. CONCLUSIONS: This course offers an appropriate and effective model that brings together an interprofessional team of experts to teach functional and clinical anatomy to medical and physical therapy students. Study results demonstrated an increase in subject-specific competencies in functional and clinical anatomy of the lower spine and hip. Medical students demonstrated the highest increase in subjective knowledge, especially in regard to clinical examination and assessment, which highlights the usefulness of this course early in the medical education. All students learned from the exchange with interprofessional group members as well as the instructors.

In Vivo Analysis of Optic Fissure Fusion in Zebrafish: Pioneer Cells, Basal Lamina, Hyaloid Vessels, and How Fissure Fusion is Affected by BMP.

Colobomata, persistent optic fissures, frequently cause congenital blindness. Here, we focused on optic fissure fusion using in vivo time-lapse imaging in zebrafish. We identified the fusion initiating cells, which we termed "pioneer cells." Based on morphology, localization, and downregulation of the neuroretinal (NR) precursor marker rx2, these cells could be considered as retinal pigment epithelial (RPE) progenitors. Notably, pioneer cells regain rx2 expression and integrate into the NR after fusion, indicating that they do not belong to the pool of RPE progenitors, supported by the lack of RPE marker expression in pioneer cells. They establish the first cellular contact between the margins in the proximal fissure region and separate the hyaloid artery and vein. After initiation, the fusion site is progressing distally, increasing the distance between the hyaloid artery and vein. A timed BMP (Bone Morphogenetic Protein) induction, resulting in coloboma, did not alter the morphology of the fissure margins, but it did affect the expression of NR and RPE markers within the margins. In addition, it resulted in a persisting basal lamina and persisting remnants of periocular mesenchyme and hyaloid vasculature within the fissure, supporting the necessity of BMP antagonism within the fissure margins. The hampered fissure fusion had severe effects on the vasculature of the eye.

Functional expression of electrogenic sodium bicarbonate cotransporter 1 (NBCe1) in mouse cortical astrocytes is dependent on S255-257 and regulated by mTOR.

The electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), is the major bicarbonate transporter expressed in astrocytes. It is highly sensitive for bicarbonate and the main regulator of intracellular, extracellular, and synaptic pH, thereby modulating neuronal excitability. However, despite these essential functions, the molecular mechanisms underlying NBCe1-mediated astrocytic response to extracellular pH changes are mostly unknown. Using primary mouse cortical astrocyte cultures, we investigated the effect of long-term extracellular metabolic alkalosis on regulation of NBCe1 and elucidated the underlying molecular mechanisms by immunoblotting, biotinylation of surface proteins, intracellular H+ recording using the H+ -sensitive dye 2',7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein, and phosphoproteomic analysis. The results showed significant downregulation of NBCe1 activity following metabolic alkalosis without influencing protein abundance or surface expression of NBCe1. During alkalosis, the rate of intracellular H+ changes upon challenging NBCe1 was decreased in wild-type astrocytes, but not in cortical astrocytes from NBCe1-deficient mice. Alkalosis-induced decrease of NBCe1 activity was rescued after activation of mTOR signaling. Moreover, mass spectrometry revealed constitutively phosphorylated S255-257 and mutational analysis uncovered these residues being crucial for NBCe1 transport activity. Our results demonstrate a novel mTOR-regulated mechanism by which NBCe1 functional expression is regulated. Such mechanism likely applies not only for NBCe1 in astrocytes, but in epithelial cells as well.

Morphogenesis and axis specification occur in parallel during optic cup and optic fissure formation, differentially modulated by BMP and Wnt.

Optic cup morphogenesis is an intricate process. Especially, the formation of the optic fissure is not well understood. Persisting optic fissures, termed coloboma, are frequent causes for congenital blindness. Even though the defective fusion of the fissure margins is the most acknowledged reason for coloboma, highly variable morphologies of coloboma phenotypes argue for a diverse set of underlying pathomechanisms. Here, we investigate optic fissure morphogenesis in zebrafish to identify potential morphogenetic defects resulting in coloboma. We show that the formation of the optic fissure depends on tissue flow movements, integrated into the bilateral distal epithelial flow forming the optic cup. On the temporal side, the distal flow translates into a ventral perpendicular flow, shaping the temporal fissure margin. On the nasal side, however, the distal flow is complemented by tissue derived from the optic stalk, shaping the nasal fissure margin. Notably, a distinct population of TGFß-signalling positive cells is translocated from the optic stalk into both fissure margins. Furthermore, we show that induced BMP signalling as well as Wnt-signalling inhibition result in morphogenetic defects of the optic fissure. Our data also indicate that morphogenesis is crucial for a proper positioning of pre-specified dorsal-ventral optic cup domains.

Recommendations of the working group of the Anatomische Gesellschaft on reduction of formaldehyde exposure in anatomical curricula and institutes.

The practice of human and veterinary medicine is based on the science of anatomy and dissection courses are still irreplaceable in the teaching of anatomy. Embalming is required to preserve body donors, for which process formaldehyde (FA) is the most frequently used and well characterized biocidal substance. Since January 2016, a new occupational exposure limit (OEL) for FA of 0.37mg/m3 issued by the European Committee on Hazardous Substances is obligatory since FA has been classified as a human 1B carcinogen. The anatomical institutes in the German-speaking region are called upon to consolidate efforts to reduce use of FA in anatomical curricula and body donations. As a result, the Anatomische Gesellschaft (AG) has formed a "Working Group for Reduction of Formaldehyde Exposure in Dissection Courses" tasked with discussion and recommendation of measures to reduce FA. Based on the assessment of the Working Group, the AG has issued an official opinion to the effect that, at this point in time, embalming of body donors without FA completely is not feasible. Therefore, a combination of approaches are to be used to reduce FA exposure, including technical and structural (architectural) adaptations, modification of protocols for fixation and preservation as well as organizational measures. One structural measure considered unavoidable is the integration of air supply and exhaust of individual dissecting tables into the ventilation system of the anatomy building. To embalm human body donors, intra-arterial perfusion fixation with up to 4% FA and a total fluid volume of 150mL/kg body weight will suffice. For animals where body weights and biology of bodies vary widely (i.e. special needs of fixation for ruminants, large animals as horses) perfusion fixation with up to 4% FA and a quantity of fixative solution of 10-15% of the body weight may be required. Preservation of body donors in storage (immersion) can be done with 40% ethanol or in a full bath preservation containing up to 2% FA. Corpse humidification in the dissecting room is possible with 2% phenoxyethanol, in each case without FA. In veterinary anatomy, microbiological burden is often higher and therefore might lead to a need of FA in long-time storage. Compliance with the current OEL in all institutes would appear to be feasible in combination with various organizational measures.

TGFß-facilitated optic fissure fusion and the role of bone morphogenetic protein antagonism.

The optic fissure is a transient gap in the developing vertebrate eye, which must be closed as development proceeds. A persisting optic fissure, coloboma, is a major cause for blindness in children. Although many genes have been linked to coloboma, the process of optic fissure fusion is still little appreciated, especially on a molecular level. We identified a coloboma in mice with a targeted inactivation of transforming growth factor ß2 (TGFß2). Notably, here the optic fissure margins must have touched, however failed to fuse. Transcriptomic analyses indicated an effect on remodelling of the extracellular matrix (ECM) as an underlying mechanism. TGFß signalling is well known for its effect on ECM remodelling, but it is at the same time often inhibited by bone morphogenetic protein (BMP) signalling. Notably, we also identified two BMP antagonists among the downregulated genes. For further functional analyses we made use of zebrafish, in which we found TGFß ligands expressed in the developing eye, and the ligand binding receptor in the optic fissure margins where we also found active TGFß signalling and, notably, also gremlin 2b (grem2b) and follistatin a (fsta), homologues of the regulated BMP antagonists. We hypothesized that TGFß is locally inducing expression of BMP antagonists within the margins to relieve the inhibition from its regulatory capacity regarding ECM remodelling. We tested our hypothesis and found that induced BMP expression is sufficient to inhibit optic fissure fusion, resulting in coloboma. Our findings can likely be applied also to other fusion processes, especially when TGFß signalling or BMP antagonism is involved, as in fusion processes during orofacial development.

[Neuroanatomy of the Visual Pathway]. / Neuroanatomie der Sehbahn.

Precise knowledge of the neuroanatomy of the visual system including the perception of visual stimuli in the retina, the transmission of visual information to other areas of the central nervous system and the processing of visual information, are most important for diagnostics of diseases, which are affecting this system. Such knowledge allows, even after just a clinical examination, already a quite precise localisation of potential lesions. The aim of this article is to illustrate the neuroanatomy of the visual system with the focus on the visual pathway and the processing of visual information. Next to the main visual pathway, also other retinofugal projections are discussed. Domains, which are important for the oculomotor system, are discussed in another article in this edition of the journal.

[Neuroanatomy of the Oculomotor System]. / Neuroanatomie des okulomotorischen Systems.

After just a clinical examination, the experienced neurologist can assign specific symptoms quite precisely to distinct lesions within the brain and other parts of the nervous system, on the basis of his neuroanatomical knowledge. This also holds true for lesions affecting the oculomotor system. The aim of this article is to give a comprehensive overview of the neuroanatomical basis of the oculomotor system, in order to facilitate the precise spatial assignment of potential lesions affecting the control of eye movements. After a brief introduction, the components of the system are discussed, including the extraocular muscles and their innervating nerves. The following section will then cover the control of eye movements and will specifically address distinct patterns of eye movements and areas within the central nervous system controlling these. This article also gives a brief overview of the intraocular muscles and their control.

Eye morphogenesis driven by epithelial flow into the optic cup facilitated by modulation of bone morphogenetic protein.

The hemispheric, bi-layered optic cup forms from an oval optic vesicle during early vertebrate eye development through major morphological transformations. The overall basal surface, facing the developing lens, is increasing, while, at the same time, the space basally occupied by individual cells is decreasing. This cannot be explained by the classical view of eye development. Using zebrafish (Danio rerio) as a model, we show that the lens-averted epithelium functions as a reservoir that contributes to the growing neuroretina through epithelial flow around the distal rims of the optic cup. We propose that this flow couples morphogenesis and retinal determination. Our 4D data indicate that future stem cells flow from their origin in the lens-averted domain of the optic vesicle to their destination in the ciliary marginal zone. BMP-mediated inhibition of the flow results in ectopic neuroretina in the RPE domain. Ultimately the ventral fissure fails to close resulting in coloboma.

Differential responsiveness of distinct retinal domains to Atoh7.

During vertebrate eye development retinal progenitor cells (RPCs) differentiate into all neural cell types of the retina. Retinal ganglion cells (RGCs) represent the first cell type to be generated. For their development, Atoh7, a basic Helix Loop Helix (bHLH) transcription factor is crucial. Atoh7 loss of function results in a massive reduction or even a total loss of RGCs. However, inconsistent results have been obtained in atoh7 gain of function experiments with respect to ganglion cell genesis, implying that the effect of Atoh7 is likely to be dependent on the competence state of the RPC. In this study we addressed the differential susceptibilities of early RPCs to Atoh7 in vivo, using medaka. Unexpectedly, we observed a largely normal development of the dorsal retina, although atoh7 was precociously expressed. However, the development of the retina close to the optic nerve head (part of the ventral retina) was disturbed severely. Photoreceptors were largely absent and the Müller glia cell number was reduced significantly. The majority of cells in this domain were ganglion cells and the abnormal development of this area affected the closure of the optic fissure resulting in coloboma.

Concerted interaction of TGF-ß and GDNF mediates neuronal differentiation.

The glial cell-line derived neurotrophic factor (GDNF) is crucial for ureteric bud morphogenesis, spermatogenesis, and development of the enteric nervous system and is a potent survival factor for various neuronal populations. However, the impact of GDNF, at least on cell survival, was found to depend strongly on the presence of transforming growth factor ß (TGF-ß). In this study, we investigate the role of TGF-ß in GDNF-induced neuronal differentiation. In a cell culture paradigm of N2aGT cells (neuroblastoma cell line), we show that TGF-ß signaling localizes the GDNF ligand-binding receptor GFRa1 to the cell surface, which is a known mechanism by which TGF-ß is able to facilitate GDNF signaling. TGF-ß-mediated GDNF signaling slightly elevated the phosphorylation state of Ret, the canonical coreceptor for the GPI-linked (glycosyl-phosphatidylinositol) GFRa1. On the basis of morphological as well as immunocytological data, we finally show that GDNF-mediated neuronal differentiation is intensified when GDNF and TGF-ß act in concert.

Glia cell line-derived neurotrophic factor mediates survival of murine sympathetic precursors.

During embryonic development, neurons are first produced in excess, and final numbers are adjusted by apoptosis at later stages. Crucial to this end is the amount of target-derived growth factor available for the neurons. By this means, the target size correctly matches the innervating neuron number. This target-derived survival has been well studied for sympathetic neurons, and nerve growth factor (NGF) was identified to be the crucial factor for maintaining sympathetic neurons at late embryonic and early postnatal stages, with a virtual complete loss of sympathetic neurons in NGF knockout (KO) mice. This indicates that all sympathetic neurons are dependent on NGF. However, also different glia cell line-derived neurotrophic factor (GDNF) KO mice consistently presented a loss of sympathetic neurons. This was the rationale for investigating the role of GDNF for sympathetic precursor/neuron survival. Here we show that GDNF is capable of promoting survival of 30% sympathetic precursors dissociated at E13. This is in line with data from GDNF KOs in which a comparable sympathetic neuron loss was observed at late embryonic stages, although the onset of the phenotype was unclear. We further present data showing that GDNF ligand and canonical receptors are expressed in sympathetic neurons especially at embryonic stages, raising the possibility of an autocrine/paracrine GDNF action. Finally, we show that GDNF also maintained neonatal sympathetic neurons (40%) cultured for 2 days. However, the GDNF responsiveness was lost at 5 days in vitro.

Molecular control of Schwann cell migration along peripheral axons: keep moving!

The development of the peripheral nervous system (PNS) is a highly dynamic process, during which motor and sensory axons innervate distal targets, such as skeletal muscles and skin. Axonal function depends critically on support from Schwann cells, the main glial cell type in the PNS. Schwann cells originate from the neural crest, migrate along outgrowing axons and associate with axons along their entire length prior to ensheathment or myelination. How axonal growth and the migration of Schwann cells is coordinated at the level of reciprocal axon-glial signaling is the fascinating subject of ongoing research. Neuregulin-1 (NRG1) type III, an axonal membrane-bound ligand for receptor tyrosine kinases of the ErbB family, acts as a "master regulator" of peripheral myelination. In addition, NRG1-ErbB signaling directs the development of the Schwann cell lineage and regulates the proliferation and survival of Schwann cells. Studies in zebrafish have identified a direct role of NRG1 type III in Schwann cell migration, but to what extend NRG1 serves a similar function in the mammalian PNS is not clear. We have employed a mouse superior cervical ganglion explant culture system, in which the migration of endogenous Schwann cells along outgrowing axons can be visualized by time-lapse imaging. Using this approach, we found that NRG1 type III-ErbB signaling regulates the colonization of distal axonal segments by Schwann cells. However, our data suggest an indirect effect of NRG1 type III-ErbB signaling via the support of Schwann cell survival in proximal axonal regions rather than a direct effect on Schwann cell motility.