Ventral Migration Research Articles

The cell surface hyaluronidase TMEM2 plays an essential role in mouse neural crest cell development and survival.

Hyaluronan (HA) is a major extracellular matrix component whose tissue levels are dynamically regulated during embryonic development. Although the synthesis of HA has been shown to exert a substantial influence on embryonic morphogenesis, the functional importance of the catabolic aspect of HA turnover is poorly understood. Here, we demonstrate that the transmembrane hyaluronidase TMEM2 plays an essential role in neural crest development and the morphogenesis of neural crest derivatives, as evidenced by the presence of severe craniofacial abnormalities in Wnt1-Cre-mediated Tmem2 knockout (Tmem2CKO) mice. Neural crest cells (NCCs) are a migratory population of cells that gives rise to diverse cell lineages, including the craniofacial complex, the peripheral nervous system, and part of the heart. Analysis of Tmem2 expression during NCC formation and migration reveals that Tmem2 is expressed at the site of NCC delamination and in emigrating Sox9-positive NCCs. In Tmem2CKO embryos, the number of NCCs emigrating from the neural tube is greatly reduced. Furthermore, linage tracing reveals that the number of NCCs traversing the ventral migration pathway and the number of post-migratory neural crest derivatives are both significantly reduced in a Tmem2CKO background. In vitro studies using Tmem2-depleted mouse O9-1 neural crest cells demonstrate that Tmem2 expression is essential for the ability of these cells to form focal adhesions on and to migrate into HA-containing substrates. Additionally, we show that Tmem2-deficient NCCs exhibit increased apoptotic cell death in NCC-derived tissues, an observation that is corroborated by in vitro experiments using O9-1 cells. Collectively, our data demonstrate that TMEM2-mediated HA degradation plays an essential role in normal neural crest development. This study reveals the hitherto unrecognized functional importance of HA degradation in embryonic development and highlights the pivotal role of Tmem2 in the developmental process.

Dorsal root ganglia, neural crest migration, and spinal cord form in snakes

The classic view of the vertebrate dorsal root ganglion is that it arises from trunk neural crest cells that migrate to positions lateral to the spinal cord, sending axons dorsally into the spinal cord and dendrites ventrally to meet with motor axons in the ventral root to form spinal nerves. As a result, the ganglion ends up lying in the dorsal root of the spinal nerve. Serial histological sections of parts of the trunk of juveniles of different snake species revealed that the ganglia lie distal to the junction of dorsal and ventral roots of spinal nerves and outside the neural canal. The anatomical position of spinal ganglia in snakes suggests that regulation of trunk neural crest migration in snakes differs from that in the model endotherms in which it has been most thoroughly explored. Dorsal roots have no distinct rootlets and the span of root entry to the spinal cord is short compared to that of ventral rootlets in the same segment. Comparing early developmental stages to juvenile spinal cords shows an increased separation of spinal nerve root sites and ventral migration of the ganglion in later development. Dorsal rami of the spinal nerves leave directly from the dorsal edge of the ganglion, and the ventral ramus leaves from the ventral tip of the ganglion. How these features relate to the developmental regulation of ganglion form and position and the extraordinary locomotor capabilities of the snake trunk are unclear.

Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma

The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood. Here, we track mesothelial origins in the lateral plate mesoderm (LPM) using zebrafish. Single-cell transcriptomics uncovers a post-gastrulation gene expression signature centered on hand2 in distinct LPM progenitor cells. We map mesothelial progenitors to lateral-most, hand2-expressing LPM and confirm conservation in mouse. Time-lapse imaging of zebrafish hand2 reporter embryos captures mesothelium formation including pericardium, visceral, and parietal peritoneum. We find primordial germ cells migrate with the forming mesothelium as ventral migration boundary. Functionally, hand2 loss disrupts mesothelium formation with reduced progenitor cells and perturbed migration. In mouse and human mesothelioma, we document expression of LPM-associated transcription factors including Hand2, suggesting re-initiation of a developmental program. Our data connects mesothelium development to Hand2, expanding our understanding of mesothelial pathologies.

Mechanical ileus and mesenteric ischemia as complications of MiniMizer-gastric-ring after laparoscopic banded Roux-en-Y-gastric bypass: A case report.

IntroductionBanded laparoscopic Roux-en-Y-gastric bypass (B-LRYGB) is a surgical technique that involves reinforcing the restriction by placing a silicone ring 2 cm above the gastrojejunostomy to prevent pouch dilation, thereby maintaining the achieved weight loss and preventing weight regain. Gastrojejunostomy stenosis, erosions, and ring-migration (slippage) are well-known complications in patients undergoing banded laparoscopic procedures. We believe that our study makes a significant contribution to the literature because, to the best of our knowledge, cranial slippage (herniation) of the alimentary limb through a non-slipped MiniMizer gastric ring after B-LRYGB as well as mesenteric ischemia because of ventral slippage have not been described before in the published literature.Presentation of caseThis study presents two rare complications in middle-aged women 26 months after B-LRYGB. The first case presented with mechanical ileus due to herniation of the alimentary limb without slippage of the MiniMizer ring. The second case involved mesenteric ischemia following ventral migration of the MiniMizer ring with herniation of the alimentary limb and its mesentery through the ring with consequent torsion of the mesentery. Both patients were managed with surgical intervention and band removal. The postoperative course was uneventful.DiscussionIn cases of MiniMizer ring complications, the presentation can be either acute or chronic. Severe mesenteric ischemia is acute and can be fatal. Patients may also present with chronic recurrent abdominal pain or mechanical ileus. The loss of mesenteric fat after successful weight loss might lead to the cranial herniation of the alimentary limb. This could also be a result of dysmotility or reverse peristalsis secondary to ectopic pacemaker cells over a fixed point (in this case, the gastrojejunostomy with the MiniMizer ring) [4,5]. A gradual herniation of the intestinal wall over the fixed point can also occur due to recurrent dietary non-adherence (such as large portions and hard consistency of the food).ConclusionA high sense of suspicion and radiological investigation are crucial factors in reaching the proper diagnosis. Further studies should be conducted to examine whether other forms of ring placement or fixation could help avoid the risk of potentially fatal complications.

Injection Reactions after Administration of Sustained-release Meloxicam to BALB/cJ, C57BL/6J, and Crl:CD1(ICR) Mice.

The sustained-release formulation of meloxicam (MSR) is a compounded NSAID that may provide pain relief for as long as 72 h after administration. MSR injection-site skin reactions have occurred in several species but have not previously been observed in mice. We investigated the development and progression of localized skin reactions after a single injection of MSR in Crl:CD1(ICR), C57BL/6J, and BALB/cJ mice. Each mouse received a subcutaneous injection of MSR (n = 60), standard-formulation meloxicam (MEL; n = 24) or saline (control; SC; n = 24) and was scored daily according to a 5-point system for erythema and mass characteristics. Mice were euthanized at either 7 or 14 d after injection and underwent postmortem analysis. MSR-treated mice had more erythematous and mass reactions than did MEL and SC mice. Mass lesions developed in 49 MSR mice (82%; 95% CI, 70% to 90%), 5 MEL animals (21%; 95% CI, 7% to 42%), and 1 SC mouse. MSR-treated BALB/cJ developed erythematous lesions less frequently than similarly treated Crl:CD1(ICR) or C57BL/6J. Lesions often were ventrolateral to the injection site. The median times to the appearance of mass and erythematous lesions were 2 d and 3 d, respectively. Histologically, the erythematous and mass reactions correlated with necrotizing to pyogranulomatous injection-site panniculitis. Inflammation severity scores at 7 and 14 d after injection were greater in the MSR-treated group than the other 2 groups. No strain- or sex-associated differences emerged except that inflammation severity scores at day 14 were higher in Crl:CD1(ICR) females than males. The character of the inflammatory response in MSR-treated mice did not differ between 7 and 14 d after injection, indicating that MSR-induced inflammation is slow to resolve. The ventral migration and delayed onset of MSR injection-site reactions could result in their being attributed to another cause or not being identified. Researchers and clinicians should be aware of the potential for slowly resolving injection-site reactions with MSR.

FGF signaling is required for chemokinesis and ventral migration of trunk neural crest cells.

Neural crest cells (NCCs) delaminate from the neural tube (NT) and migrate ventrally to generate the trunk peripheral nervous system (PNS). Although several signaling pathways have been identified that steer NCCs once they are on their ventral trajectory, no molecules have been identified that are required for the initial migration between the NT and the dorsal root ganglion. Given the critical role of fibroblast growth factor (FGF) signaling in embryogenesis, we investigated its function in this initial migration. FGFR1 signaling is required for the migration of newly delaminated NCCs onto the ventral pathway. Live imaging of migrating NCCs revealed that inhibition of FGFR1 signaling caused the dorsally stalled NCCs to lose their dorsal/ventral oriented polarity and instead adopt a rounded morphology while dynamically extending filopodia. FGF8, an FGFR1 ligand, increased motility of NCCs away from the NT by acting chemokinetically. Finally, we provide evidence that inhibition of FGFR1-mediated chemokinesis is partially rescued by increasing Akt signaling, inhibiting RhoA, and activation of N-cadherin signaling. These data support a model in which NCCs are stimulated chemokinetically by FGF:FGFR1 signaling, and that this activation positions and orients NCCs on their ventral migratory route-a process that is essential for patterning the trunk PNS.

Sli is required for proper morphology and migration of sensory neurons in the Drosophila PNS

Neurons and glial cells coordinate with each other in many different aspects of nervous system development. Both types of cells are receiving multiple guidance cues to guide the neurons and glial cells to their proper final position. The lateral chordotonal organs (lch5) of the Drosophila peripheral nervous system (PNS) are composed of five sensory neurons surrounded by four different glial cells, scolopale cells, cap cells, attachment cells and ligament cells. During embryogenesis, the lch5 neurons go through a rotation and ventral migration to reach their final position in the lateral region of the abdomen. We show here that the extracellular ligand sli is required for the proper ventral migration and morphology of the lch5 neurons. We further show that mutations in the Sli receptors Robo and Robo2 also display similar defects as loss of sli, suggesting a role for Slit-Robo signaling in lch5 migration and positioning. Additionally, we demonstrate that the scolopale, cap and attachment cells follow the mis-migrated lch5 neurons in sli mutants, while the ventral stretching of the ligament cells seems to be independent of the lch5 neurons. This study sheds light on the role of Slit-Robo signaling in sensory neuron development.

PHACES syndrome with Ectopia cordis

PHACES syndrome is an acronym for, P, posterior fossa anomalies as Dandy- Walker malformation; H, hemangioma (capillary segmental faces); A, arterial lesions of the head and neck (the most common ones include aberrant origin or course, hypoplasia, dysplasia and agenesis); C, cardiac abnormalities as coarctation of aorta; E, abnormalities of the eye and S, sternal defect. The constellation of findings of PHACES syndrome may vary significantly in different patients. Complete sternal cleft with ectopia cordis is an extremely rare congenital anomaly failed ventral migration and fusion of the two-lateral mesodermal sternal bands between the sixth and ninth weeks of gestation. We are reporting a rare case of PHACES syndrome, with partial ectopia cordis as a midline defect, who is in our follow up since birth. Survival of the child without surgical intervention with epithelialization over the defect and Leucomatous corneal opacity are interesting findings.

Commissural neurons transgress the CNS/PNS boundary in absence of ventricular zone-derived netrin 1.

During the development of the central nervous system (CNS), only motor axons project into peripheral nerves. Little is known about the cellular and molecular mechanisms that control the development of a boundary at the CNS surface and prevent CNS neuron emigration from the neural tube. It has previously been shown that a subset of spinal cord commissural axons abnormally invades sensory nerves in Ntn1 hypomorphic embryos and Dcc knockouts. However, whether netrin 1 also plays a similar role in the brain is unknown. In the hindbrain, precerebellar neurons migrate tangentially under the pial surface, and their ventral migration is guided by netrin 1. Here, we show that pontine neurons and inferior olivary neurons, two types of precerebellar neurons, are not confined to the CNS in Ntn1 and Dcc mutant mice, but that they invade the trigeminal, auditory and vagus nerves. Using a Ntn1 conditional knockout, we show that netrin 1, which is released at the pial surface by ventricular zone progenitors is responsible for the CNS confinement of precerebellar neurons. We propose, that netrin 1 distribution sculpts the CNS boundary by keeping CNS neurons in netrin 1-rich domains.

Non-cell autonomous control of precerebellar neuron migration by Slit and Robo proteins.

During development, precerebellar neurons migrate tangentially from the dorsal hindbrain to the floor plate. Their axons cross it but their cell bodies stop their ventral migration upon reaching the midline. It has previously been shown that Slit chemorepellents and their receptors, Robo1 and Robo2, might control the migration of precerebellar neurons in a repulsive manner. Here, we have used a conditional knockout strategy in mice to test this hypothesis. We show that the targeted inactivation of the expression of Robo1 and Robo2 receptors in precerebellar neurons does not perturb their migration and that they still stop at the midline. The selective ablation of the expression of all three Slit proteins in floor-plate cells has no effect on pontine neurons and only induces the migration of a small subset of inferior olivary neurons across the floor plate. Likewise, we show that the expression of Slit proteins in the facial nucleus is dispensable for pontine neuron migration. Together, these results show that Robo1 and Robo2 receptors act non-cell autonomously in migrating precerebellar neurons and that floor-plate signals, other than Slit proteins, must exist to prevent midline crossing.

Origin of the Lateral Wall of the Mammalian Skull: Fossils, Monotremes and Therians Revisited

To interpret the fundamental differences in the structure and origin of the braincase sidewalls of monotremes, multituberculates, and therians, we examined MicroCT scans of a mammaliaform, Morganucodon; two non-mammalian cynodonts, Massetognathus and Probainognathus; a stem therian, Vincelestes; a juvenile and adult monotreme, Ornithorhynchus; and two marsupials, Monodelphis and Didelphis. The skull of Morganucodon resembles the pattern predicted for an early mammal: the descending flanges of the frontal and parietal cover the lateral surface of the orbitosphenoid and the palatine forms most of the medial wall of the orbit. In monotremes, the lateral region of the chondrocranium ossifies to form a long presphenoid/orbitosphenoid complex. During the transition from early mammals to extant mammals the height of the alisphenoid decreased drastically, the anterior lamina extended anteriorly to form part of the sidewall while the lateral surface of the orbitosphenoid was exposed by the dorsal withdrawal of the frontal and parietal. By contrast, in multituberculates and therians the lateral edges of the frontals extended further ventrally and the orbitosphenoid was reduced to a smaller orbital exposure below the frontals. In multituberculates the alisphenoid decreased in height, replaced by an anterior extension of the anterior lamina. The palatine withdrew from the orbital wall, replaced by a dorsally directed expansion of the maxilla. Extant therians have lost the anterior lamina. The inferior edges of the frontal followed the further ventral migration of the orbitosphenoid. The alisphenoid and parietal form most of the braincase sidewall.

An exclusive cellular and molecular network governs intestinal smooth muscle cell differentiation in vertebrates.

Intestinal smooth muscle cells (iSMCs) are a crucial component of the adult gastrointestinal tract and support intestinal differentiation, peristalsis and epithelial homeostasis during development. Despite these crucial roles, the origin of iSMCs and the mechanisms responsible for their differentiation and function remain largely unknown in vertebrates. Here, we demonstrate that iSMCs arise from the lateral plate mesoderm (LPM) in a stepwise process. Combining pharmacological and genetic approaches, we show that TGFβ/Alk5 signaling drives the LPM ventral migration and commitment to an iSMC fate. The Alk5-dependent induction of zeb1a and foxo1a is required for this morphogenetic process: zeb1a is responsible for driving LPM migration around the gut, whereas foxo1a regulates LPM predisposition to iSMC differentiation. We further show that TGFβ, zeb1a and foxo1a are tightly linked together by miR-145 In iSMC-committed cells, TGFβ induces the expression of miR-145, which in turn is able to downregulate zeb1a and foxo1a The absence of miR-145 results in only a slight reduction in the number of iSMCs, which still express mesenchymal genes but fail to contract. Together, our data uncover a cascade of molecular events that govern distinct morphogenetic steps during the emergence and differentiation of vertebrate iSMCs.

IMAGING STUDY ON LUMBAR PLEXUS BY MINIMALLY INVASIVE LATERAL TRANSPSOAS APPROACH

To analyze the relative position between lumbar plexus and access corridor of minimally invasive lateral transpsoas approach based on magnetic resonance imaging distribution of lumbar plexus by three dimensional reconstruction technique, so as to evaluate approach safety. Three-dimensional fast imaging employing steady-state acquisition sequences of lumbar spine were performed on 71 patients with lumbar degenerative diseases between July 2012 and January 2015. The axial image distance between the anterior edge of lumbar plexus and sagittal central perpendicular line (SCPL) of disc was determined using the distance formula at the mid-disc space from L1, 2 to L4, 5 level. SCPL was drawn perpendicularly to the sagittal plane of intervertebral disc and it passed through its central point, which is initial dilator trajectory for transpsoas approach. With respect to the SCPL of disc, the distance with a positive value indicated neural tissue posterior to it whereas anterior to it represented by a negative value. Various branches of lumbar plexus which passed through the psoas major anterior to the SCPL of disc were identified in 42 (59.2%), 58 (81.7%), and 70 (98.6%) patients at L2, 3, L3, 4, and L4, 5 levels, respectively. It is possible to infer the presence of genitofemoral nerve in accordance with relevant anatomic research. A ventral migration of intrapsoas nerves is identified from L1, 2 to L4, 5 level. All differences between levels were statistically significant (P<0.05). With respect to the SCPL of disc, a pass way of guide wire or a radiographic reference landmark to place working channel, lumbar plexus lie posterior to it from L1, 2 to L3, 4 level and shift anteriorly to it at L4, 5 level, while genitofemoral nerve locate anterior to the SCPL from L2, 3 to L4, 5 level. Neural retraction may take place during sequential dilation of working channel especially at L4, 5 level.

Paper #35 Ventral Rod Migration of Posteriorly Applied Growing Rod Technology for Early Onset Scoliosis

As growing rod technology evolves, we discover complications of it’s use previously undescribed. Ventral rod migration(VRM) is a potentially catastrophic complication of growing rods. We defined VRM as ventral movement > 2 mm at the kyphotic apex, plotted from the posterior dorsal cortex of the apical lamina on axial CT. A review of CT imaging was conducted to assess for unidentified evidence of VRM. VRM was demonstrated in 3 patients, 1 of whom demonstrated rods positioned within the spinal canal.

Pentalogía de Cantrell. Reporte de caso

The pentalogy of Cantrell is a congenital anomaly characterized by variable association of a thoracoabdominal wall defect to defect of the lower sternum, diaphragm, pericardium and heart, the most representative is ectopia cordis. Cantrell in 1958 reported 5 cases with this anomaly. The prevalence of pentalogy of Cantrell has been estimated between 1 / 65, 000 to 1 in 200,000 live births. The etiology of this anomaly is not clear and is considered heterogeneous. The mechanism proposed embriopatologico suggests a flaw in the ventral migration of mesodermal cells. We report a case of pentalogy of Cantrell with all the classic features with prenatal diagnosis. It also suggests a hypothesis about the embriopatogenesis and integrated management of the mother and fetus.

GABA modulation of SVZ-derived progenitor ventral cell migration.

The subventricular zone (SVZ) is a proliferative region that provides neurons to olfactory bulb throughout life. The new neurons undergo cell migration from SVZ and travel until they reach their final destination. We previously showed in the early postnatal mouse a ventral migratory subpopulation from SVZ targets the Islands of Calleja (ICC) in the basal forebrain. However, unlike the well-characterized rostral migratory stream, little is known about the guidance mechanisms operating in the ventrally directed migratory pathway. In this study, we examined the role of neurotransmitter γ-aminobutyric acid (GABA) in SVZ-derived progenitor ventral migration and the involvement of this neurotransmitter in the cytoarchitectual organization of dispersed cells into the tight clusters of the ICC. Our results show that the ventral SVZ cell migration rate was enhanced by GABA acting through a GABAA receptor and that GABA acts as a directional guidance cue for ventral migrating cells. Furthermore, disruption of GABA signaling inhibited the formation of Island clusters in vitro. Taken together, these data suggest that GABA is an important guidance and organizational cue for the Island of Calleja.

Establishment of Gal4 transgenic zebrafish lines for analysis of development of cerebellar neural circuitry

The cerebellum is involved in some forms of motor coordination and motor learning. Here we isolated transgenic (Tg) zebrafish lines that express a modified version of Gal4-VP16 (GFF) in the cerebellar neural circuits: granule, Purkinje, or eurydendroid cells, Bergmann glia, or the neurons in the inferior olive nuclei (IO) which send climbing fibers to Purkinje cells, with the transposon Tol2 system. By combining GFF lines with Tg lines carrying a reporter gene located downstream of Gal4 binding sequences (upstream activating sequence: UAS), we investigated the anatomy and developmental processes of the cerebellar neural circuitry. Combining an IO-specific Gal4 line with a UAS reporter line expressing the photoconvertible fluorescent protein Kaede demonstrated the contralateral projections of climbing fibers. Combining a granule cell-specific Gal4 line with a UAS reporter line expressing wheat germ agglutinin (WGA) confirmed direct and/or indirect connections of granule cells with Purkinje cells, eurydendroid cells, and IO neurons in zebrafish. Time-lapse analysis of a granule cell-specific Gal4 line revealed initial random movements and ventral migration of granule cell nuclei. Transgenesis of a reporter gene with another transposon Tol1 system visualized neuronal structure at a single cell resolution. Our findings indicate the usefulness of these zebrafish Gal4 Tg lines for studying the development and function of cerebellar neural circuits.

Abstract LB-38: Zebrafish embryos provide a permissive environment for the growth and dissemination of primary human myeloma and its precursor cells

Abstract Existing animal models do not support the growth and dissemination of purified patient myeloma cells, a significant obstacle to the study of their biological behavior and the identification of pathways that might be targeted therapeutically. We report here that zebrafish embryos do support the growth of myeloma cells. This study was designed to compare the host angiogenic response and the growth and dissemination of CD138+ plasma cells derived from the bone marrow of patients with primary and relapsed myeloma to CD138+ cells from patients with the pre-myelomatous conditions monoclonal gammopathy of uncertain significance (MGUS) and smoldering myeloma. Fifty to 100 primary myeloma or myeloma precursor cells suspended in Matrigel and labeled with the red fluorescent indocarbocyanine dye DiI were injected into the perivitelline space of zebrafish embryos 48 hours after fertilization and the embryos observed for up to 7 days after injection. We used Tg(fli1:GFP) zebrafish bred on a Casper (albino) background to monitor host angiogenesis. Cells from primary and relapsed myeloma patients induced intense angiogenesis with ventral migration of vascular sprouts from the ipsilateral sub-intestinal venous system into the Matrigel plug, as well as rapid growth of the injected cells. In 70% of the injected embryos, CD138+ cells from myeloma patients formed a large red fluorescent cell mass and some or all of the cells exited the Matrigel plug and disseminated throughout the embryo. In contrast, CD138+ cells from patients with MGUS or smoldering myeloma did not induce angiogenesis and did not grow or disseminate. When purified human or zebrafish VEGF was added to a Matrigel plug containing MGUS cells, they behaved like cells isolated from patients with myeloma - forming a tumor mass and exiting the Matrigel plug. In contrast, CD138+ cells from normal individuals did not proliferate or disseminate, even when exposed to exogenous VEGF. To the best of our knowledge, this is the first study to compare the behavior of plasma cells isolated from myeloma and pre-myeloma patients in zebrafish embryos, which allow for direct observation of cell behavior in real time. The most important finding is that there is an absolute requirement for VEGF which changes the behavior of clonal cells derived from MGUS patients and makes them indistinguishable from cells derived from patients with clinical myeloma. This finding challenges the prevailing dogma that conversion from MGUS to myeloma is due to the acquisition of one or more “driver” mutations that favor proliferation and dissemination of a previously indolent cell population. Our data suggest that exposure to a host humoral factor can also induce this transformation. To the best of our knowledge, this is the first demonstration of the conversion of a pre-malignant to a malignant cell in myeloma or any other tumor by in vivo manipulation of the host environment. This change in phenotype, may not be unique to MGUS and suggests a new paradigm for assessing the transformation of other pre-malignant disorders, like Barrett's esophagus or ductal carcinoma in situ (DCIS) of the breast. Our data provides evidence that it is possible to induce “primed” pre-malignant cells to acquire a “malignant” phenotype by delivering blood borne factors to dormant or slowly growing cells. Citation Format: Dongdong MA, Arinze Nwokeji, Jianhong Lin, Yu-Tzu Tai, Nikhil Munshi, Robert I. Handin. Zebrafish embryos provide a permissive environment for the growth and dissemination of primary human myeloma and its precursor cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-38. doi:10.1158/1538-7445.AM2014-LB-38

Discrete levels of Twist activity are required to direct distinct cell functions during gastrulation and somatic myogenesis.

Twist (Twi), a conserved basic helix-loop-helix transcriptional regulator, directs the epithelial-to-mesenchymal transition (EMT), and regulates changes in cell fate, cell polarity, cell division and cell migration in organisms from flies to humans. Analogous to its role in EMT, Twist has been implicated in metastasis in numerous cancer types, including breast, pancreatic and prostate. In the Drosophila embryo, Twist is essential for discrete events in gastrulation and mesodermal patterning. In this study, we derive a twi allelic series by examining the various cellular events required for gastrulation in Drosophila. By genetically manipulating the levels of Twi activity during gastrulation, we find that coordination of cell division is the most sensitive cellular event, whereas changes in cell shape are the least sensitive. Strikingly, we show that by increasing levels of Snail expression in a severe twi hypomorphic allelic background, but not a twi null background, we can reconstitute gastrulation and produce viable adult flies. Our results demonstrate that the level of Twi activity determines whether the cellular events of ventral furrow formation, EMT, cell division and mesodermal migration occur.

A MRI study of lumbar plexus in patients with degenerative lumbar scoliosis after extreme lateral interbody fusion

To analyze the magnetic resonance neural imaging distribution of lumbar plexus in patients with degenerative lumbar scoliosis and evaluate its value and the safety of extreme lateral interbody fusion (XLIF). Three-dimensional fast imaging employing steady-state acquisition (3D FIESTA) sequences of lumbar spine were scanned on 19 patients with degenerative lumbar scoliosis, including levo scoliosis (n = 11) and dextro scoliosis (n = 8). All images were sent to workstation for multiplanar volume reconstruction to analyze the distribution of lumbar plexus from L1-2 to L4-5 level. The axial image distance (AID) was measured between anterior edge of lumbar plexus and sagittal central perpendicular line (SCPL). SCPL was drawn perpendicularly to the sagittal plane of intervertebral disc and passed through its central point. It was actually the pathway of guide wire implanting procedure and the ongoing axis of work channel during XLIF. With respect to SCPL, the distance with a positive value indicated posterior neural tissue whereas a negative value anterior neural tissue. The differences of AID were compared between convex and concave sides and among different cases and levels. From L1-2 to L4-5 level, the AID on the concave side in levo scoliosis or dextro scoliosis cases was (13.7 ± 2.5) mm/ (12.9 ± 5.5) mm, (8.3 ± 4.7) mm/ (8.5 ± 5.7) mm, (2.7 ± 3.6) mm/ (2.5 ± 7.2) mm and (-4.2 ± 3.8) mm/ (-3.8 ± 7.1) mm respectively. They were located significantly posteriorly to the relevant disc compared to those on the convex side at the same intervertebral space (P < 0.05). The differences of AID at the same side, concave or convex side, was significant (P < 0.05). No significant differences of lumbar plexus distribution existed between levo scoliosis and dextro scoliosis cases (P > 0.05). Lumbar plexus passes through psoas posteriorly to SCPL on both side at L1-2, L2-3 level and on the concave side at L3-4 level. And they shift anteriorly to SCPL on the convex side at L3-4 level and on both sides at L4-5 level. It indicates a ventral migration of lumbar plexus from L1-2 to L4-5 level. Preoperative magnetic resonance neural imaging is valuable for assessing the safety of XLIF approach. Operation from the concave may reduce the risk of injury to lumbar plexus.