![\"flerkobardos\"](\"https:\/\/semmelweis.hu\/stemcell\/files\/2021\/09\/1632491971116-400x265.jpg\")
<\/p>\nLaborat\u00f3riumunk minden tagja r\u00e9szt vett id\u00e9n a Magyar Anat\u00f3mus T\u00e1rsas\u00e1g 2021. \u00c9vi Konferenci\u00e1j\u00e1n, mely id\u00e9n Budapesten az \u00c1llatorvostudom\u00e1nyi Egyetemen Prof. S\u00f3tonyi P\u00e9ter rektor \u00far szervez\u00e9s\u00e9vel szeptember 17-\u00e9n \u00e9s 18-\u00e1n ker\u00fclt lebonyol\u00edt\u00e1sra. A tudom\u00e1nyos programban 6 el\u0151ad\u00e1ssal \u00e9s 4 poszterrel vett\u00fcnk r\u00e9szt. Dr. Nagy N\u00e1ndor tov\u00e1bb\u00e1 a Flerk\u00f3-B\u00e1rdos Eml\u00e9k\u00e9rem (Szenior Kateg\u00f3ria 2021. \u00e9vi nyertese) kit\u00fcntet\u00e9st vehette \u00e1t.<\/p>\n
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A megfelel\u0151en szab\u00e1lyozott glia-eredet\u0171 n\u00f6veked\u00e9si faktor (GDNF), illetve ezt megk\u00f6t\u0151 RET tirozin kin\u00e1z t\u00edpus\u00fa receptor \u00e1ltal medi\u00e1lt jel\u00e1tviteli folyamat d\u00f6nt\u0151 fontoss\u00e1g\u00fa a ganglionl\u00e9c eredet\u0171 \u0151ssejtek migr\u00e1ci\u00f3ja, prolifer\u00e1ci\u00f3ja \u00e9s differenci\u00e1l\u00f3d\u00e1sa sor\u00e1n. A RET receptor hi\u00e1nya ganglionmentes b\u00e9l kialakul\u00e1s\u00e1hoz (Hirschsprung-k\u00f3r) vezet, m\u00edg a t\u00falm\u0171k\u00f6d\u0151 RET multiplex endokrin neopl\u00e1zia (MEN) szindr\u00f3m\u00e1t okozhat. Egyes RET-mut\u00e1ci\u00f3k az intestinalis aganglionosis, \u00e9s a MEN szindr\u00f3m\u00e1hoz t\u00e1rsul\u00f3 tumorokban egyar\u00e1nt el\u0151fordulnak. Ez a RET receptorhoz kapcsolhat\u00f3 l\u00e1tsz\u00f3lag paradox fenot\u00edpus egy „Janus-mut\u00e1ci\u00f3” felt\u00e9telez\u00e9s\u00e9hez vezetett, amely a RET-aktivit\u00e1s fokoz\u00f3d\u00e1s\u00e1t vagy k\u00e1rosod\u00e1s\u00e1t okozza a sejtk\u00f6rnyezett\u0151l f\u00fcgg\u0151en. A GDNF \u00e1ltal k\u00f6zvet\u00edtett RET-aktiv\u00e1ci\u00f3 hat\u00e1s\u00e1nak vizsg\u00e1lata sor\u00e1n embryon\u00e1lis b\u00e9lszakaszok ex vivo teny\u00e9szt\u00e9si rendszer\u00e9ben diszt\u00e1lis ganglionmentes vastagb\u00e9l \u00e9s ganglioneurom\u00e1k egyidej\u0171 kialakul\u00e1s\u00e1t mutattuk ki. \u00c9rdekes m\u00f3don a GDNF-stimul\u00e1ci\u00f3 \u00e1ltal kiv\u00e1ltott tumorok olyan enter\u00e1lis neuron\u00e1lis progenitorokat tartalmaznak, amelyek k\u00e9pesek az enter\u00e1lis idegrendszer rekonstru\u00e1l\u00e1s\u00e1ra, ha norm\u00e1lis fejl\u0151d\u00e9si k\u00f6rnyezetbe transzplant\u00e1ljuk \u0151ket. Ezek a k\u00eds\u00e9rleti eredm\u00e9nyek azt sugallj\u00e1k, hogy nem felt\u00e9tlen\u00fcl sz\u00fcks\u00e9ges Janus-mut\u00e1ci\u00f3 a Hirschsprung-k\u00f3r \u00e9s a MEN-asszoci\u00e1lt tumorok egy\u00fcttes el\u0151fordul\u00e1s\u00e1hoz, hanem a RET-stimul\u00e1ci\u00f3 \u00f6nmag\u00e1ban elegend\u0151 mindk\u00e9t fenot\u00edpus kialakul\u00e1s\u00e1hoz. Az eredm\u00e9nyek felvetik azt a lehet\u0151s\u00e9get, hogy a ganglioneurom\u00e1kb\u00f3l izol\u00e1lt tumorsejteket a ganglionmentess\u00e9ggel jellemzett neurocristopathiak gy\u00f3gy\u00edt\u00e1s\u00e1ra alkalmazzuk.<\/p>\n<\/div>\n<\/div>\n
Az \u00e1ltalunk bemutatott tov\u00e1bbi el\u0151ad\u00e1sok \u00e9s poszterek absztraktjai:<\/p>\n
The intestine is innervated by intrinsic neurons of the enteric nervous system (ENS) and by the afferent and efferent axons of peripheral ganglia. The nerve of Remak (NoR) is a sacral neural crest-derived (NCC) structure, an avian-specific ganglionated structure that extends from the cloaca to the proximal midgut and has role in extrinsic innervation of the gut. Development of NoR starts at early embryonic day 5 (E5) and axons projecting from the NoR reach the gut wall at E7. The molecular mechanism of NoR-derived axon growth is unknown. In mammals the presence of CXCR4, a cell surface receptor for the chemokine stromal cell-derived factor-1 (SDF1, also named CXCL12) is responsible for several embryonic developmental processes in response to CXCL12 including migration of neural crest cells, neuronal survival and axon pathfinding. We have employed chimeric tissue recombination, in situ hybridization, combined with immunofluorescence labeling to follow the precise spatiotemporal expression of CXCR4 molecule during migration of sacral NCC within the ENS. We have observed specific CXCR4 expression in NoR and CXCL12 in the mesenchyme around of NoR and pelvic plexus. Embryonic hindgut+NoR cultured in presence of CXCL12 results in significant increase of NCC migration and axon projection from the NoR, while inhibition of CXCR4 signaling with AMD3100 disrupt their migration out of explant, suggesting a novel role for CXCR4\/CXCL12 signaling in the extrinsic innervation of the colorectum.
\nGrant: NKFI 124740<\/p>\n<\/div>\n<\/div>\n
A complex sz\u00edvfejl\u0151d\u00e9si rendelleness\u00e9ggel sz\u00fcletett gyermekek \u00e9let\u00fck els\u0151 h\u00f3napjaiban \u00e9letment\u0151 sz\u00edvm\u0171t\u00e9tere szorulhatnak, melyek sor\u00e1n sokszor, a csecsem\u0151mirigy m\u00e9rete \u00e9s elhelyezked\u00e9se miatt a seb\u00e9sz tot\u00e1lis thymectomiara k\u00e9nyszer\u00fcl. A thymectomia r\u00f6vid t\u00e1v\u00fa k\u00f6vetkezm\u00e9nyei nem ismertek az immunrendszer m\u0171k\u00f6d\u00e9s\u00e9ben, azonban hossz\u00fa t\u00e1von autoimmun folyamatok, allergi\u00e1s reakci\u00f3k, vagy ak\u00e1r daganatos megbeteged\u00e9sek is kialakulhatnak. Munk\u00e1nk sor\u00e1n gyermek sz\u00edvseb\u00e9szeti m\u0171t\u00e9tekb\u0151l sz\u00e1rmaz\u00f3 thymusokat vizsg\u00e1ltunk immuncitok\u00e9miai \u00e9s elektronmikroszk\u00f3pos technik\u00e1kkal, valamint a perif\u00e9ri\u00e1s v\u00e9r analiz\u00e1l\u00e1s\u00e1t v\u00e9gezt\u00fck \u00e1raml\u00e1si citometri\u00e1val. A thymus alapv\u00e1z\u00e1t az endoderm\u00e1lis eredet\u0171 h\u00e1mretikulum sejtek alkotj\u00e1k, melyek a k\u00e9reg\u00e1llom\u00e1nyban cytokeratin pozit\u00edv h\u00e1l\u00f3zatot k\u00e9peznek, ahol az adapt\u00edv immunit\u00e1s kialakul\u00e1s\u00e1hoz sz\u00fcks\u00e9ges hemopoietikus eredet\u0171 T-sejtek fejl\u0151dnek. Mint\u00e1inkban elt\u00e9r\u0151 sz\u00edvfejl\u0151d\u00e9si rendelleness\u00e9gek mellett a thymus abnorm\u00e1lis morfol\u00f3gi\u00e1j\u00e1t tal\u00e1ltuk: a k\u00e9reg\u00e1llom\u00e1nyban a T limfocit\u00e1k pozit\u00edv szelekci\u00f3j\u00e1ban r\u00e9sztvev\u0151 h\u00e1msejtek cytokeratin negat\u00edvak \u00e9s a thymus h\u00e1msejtekre specifikus Foxn-1 transzkripci\u00f3s faktor expresszi\u00f3ja is megsz\u0171nik. Elektronmikroszk\u00f3pos megfigyel\u00e9seink szerint ezen sejtekben degenerat\u00edv folyamatokra jellemz\u0151 morfol\u00f3gia figyelhet\u0151 meg, miszerint a citoplazm\u00e1ban megn\u0151 a vakuol\u00e1k sz\u00e1ma, a mitokondriumok bels\u0151 krist\u00e1lyos szerkezete \u00e9s a sejtmag kromatin\u00e1llom\u00e1nya is felbomlik. A h\u00e1msejtek mellett a thymus vaszkulariz\u00e1ci\u00f3ja is s\u00e9r\u00fcl, mely feltehet\u0151leg a Foxn-1 hi\u00e1nya k\u00f6vetkezt\u00e9ben alakulhat ki, hiszen a thymus h\u00e1msejtek keratiniz\u00e1ci\u00f3j\u00e1t \u00e9s a vaszkulariz\u00e1ci\u00f3t is ezen transzkripci\u00f3s faktor ir\u00e1ny\u00edtja. A h\u00e1msejtek termin\u00e1lis differenci\u00e1l\u00f3d\u00e1s\u00e1hoz, valamint megfelel\u0151 m\u0171k\u00f6d\u00e9s\u00fckh\u00f6z a h\u00e1msejtek interakci\u00f3ja sz\u00fcks\u00e9ges a ganglionl\u00e9cb\u0151l sz\u00e1rmaz\u00f3 mesenchym\u00e1val. Felt\u00e9telezz\u00fck, hogy az abnorm\u00e1lisan fejl\u0151d\u0151 thymus kialakul\u00e1sa egy, a k\u00fcl\u00f6nb\u00f6z\u0151 sz\u00edvfejl\u0151d\u00e9si rendelleness\u00e9gekkel p\u00e1rhuzamosan megjelen\u0151 k\u00f3rk\u00e9p. Azon k\u00e9rd\u00e9s megv\u00e1laszol\u00e1s\u00e1ra, hogy egy adott sz\u00edvfejl\u0151d\u00e9si rendelleness\u00e9ggel sz\u00fcletett gyermek k\u00f6zponti nyirokszerve partialisan, tot\u00e1lisan vagy egy\u00e1ltal\u00e1n el legyen-e t\u00e1vol\u00edtva, tov\u00e1bbi vizsg\u00e1latokra van sz\u00fcks\u00e9g.<\/p>\n<\/div>\n<\/div>\n
The enteric nervous system (ENS), which is derived from enteric neural crest cells (ENCCs) during gut development, represents the neuronal innervation of the gastrointestinal tract and is critical for regulating normal intestinal function. Compromised ENCC migration can lead to Hirschsprung Disease, which is characterized by an aganglionic distal bowel. We find that removal of the ceca, a paired structure present at the midgut-hindgut junction in avian intestine, leads to severe hindgut aganglionosis, suggesting that the ceca are required for ENS development. To test this, we replaced the ceca of embryonic day 6 (E6) wild-type chicks with ceca from transgenic GFP chicks. Interestingly, the entire hindgut ENS arises from the GFP+ ceca-derived ENCC population. Comparative transcriptome profiling of the cecal buds compared to the interceca region shows that the non-canonical Wnt signaling pathway is preferentially expressed within the ceca. Specifically, Wnt11 is highly expressed in the ceca, as confirmed by RNA in situ hybridization, leading us to hypothesize that cecal expression of Wnt11 is important for ENCC colonization of the hindgut. Organ cultures were prepared using E6 avian intestine, when ENCCs are migrating through the ceca, and showed that Wnt11 inhibits enteric neuronal differentiation. These results reveal an essential role for the ceca during hindgut ENS formation and highlight an important function for non-canonical Wnt signaling in regulating ENCC differentiation and thereby promoting their migration into the colon.<\/p>\n<\/div>\n<\/div>\n
Neuroinflammation in the gut is associated with many gastrointestinal (GI) diseases, including inflammatory bowel disease. In the brain, neuroinflammatory conditions are associated with blood-brain barrier (BBB) disruption and subsequent neuronal injury. We sought to determine whether the enteric nervous system (ENS) is similarly protected by a physical barrier and whether that barrier is disrupted in colitis. We identified a blood-myenteric barrier (BMB) consisting of ECM proteins (agrin and collagen-4) and glial end-feet, reminiscent of the BBB, surrounded by a collagen-rich periganglionic space (PGS). The BMB is impermeable to the passive movement of 4 kDa FITC-dextran particles. A population of macrophages is present within enteric ganglia (intraganglionic macrophages, IGMs) and exhibits a distinct morphology from muscularis macrophages (MMs), with extensive cytoplasmic vacuolization and mitochondrial swelling, but without signs of apoptosis. IGMs can penetrate the BMB in physiological conditions and establish direct contact with neurons and glia. DSS-induced colitis leads to BMB disruption, loss of its barrier integrity, and increased numbers of IGMs in a macrophage-dependent process. In intestinal inflammation, macrophage-mediated degradation of the BMB disrupts its physiologic barrier function, eliminates the separation of the intra- and extra-ganglionic compartments, and allows inflammatory stimuli to access the myenteric plexus. This suggests a potential mechanism for the onset of neuroinflammation in colitis and other GI pathologies with acquired enteric neuronal dysfunction.<\/p>\n<\/div>\n<\/div>\n
The avian bursa of Fabricius (BF) is a primary lymphoid organ, critical to normal B-lymphocyte development. During embryogenesis the epithelial anlage of the BF emerges as a diverticulum of the cloaca surrounded by undifferentiated mesenchyme. While it is believed that CD45+ hematopoietic stem cells colonize the epithelial-mesenchymal primordium that would provide a selective microenvironment for B cell precursor expansion, it is more likely that separate B-cell, macrophage, dendritic cell precursors colonize the mesenchyme, and some precursors migrate to the surface epithelium initiating lymphoid follicle bud formation. The goal of this project is to characterize the developmental mechanisms of lymphoid follicle formation using a large panel of monoclonal antibodies (mAbs) specific for leukocytes (CD45), B-cells (chB6, EIVE12), macrophages (TIM4), bursal dendritic cells (CSF1R). The staining of embryonic BF by these mAbs helps to distinguish between three different lineages of hematopoietic cells. CD45+\/EIVE12+ cells were first observed in the BF rudiment, many of them enter the surface epithelium to induce follicle bud formation. This will be colonized by the second cell type that belong to the CSF1R+\/TIM4+ population, followed by chB6+ B cell precursors. In conclusion, we could determine three different types of precursors which colonize the embryonic BF, indicating that there is a pre-bursal segregation between these blood-borne cell lineages. Using chick-duck chimeras, we demonstrate that the first cell types which enter the bursal epithelium are not the dendritic\/macrophages or B cell precursors, but are a transient lymphoid bud inducer cell population whose primary role is to induce follicle bud formation.<\/p>\n<\/div>\n<\/div>\n
The bursa of Fabricius (BF) is a primary lymphoid organ, unique in birds, that is responsible for the development of B cells within its follicular microenvironment. The bursal lymphoid follicles consist of two histologically and embryological distinct compartments: the ectodermal medulla and the cortex of mesodermal origin. Despite the fact that the histology of the follicular medulla is well characterized, the morphology of the ontogenetically later emerging cortex is less clear. In this study, we describe the molecular composition and ontogeny of the BF follicular cortex. In contrast to medulla, the adult cortical CD45+\/chB6+ B-lymphocytes express surface CXCR4. In the cortex the reticular cells produce extracellular matrix (ECM) rich in proteoglycans, collagens, and glycoproteins, unlike the medulla where there is no detectable ECM. Characterization of the ECM showed that compared to most of the ECM proteins, expression of Tenascin-C can be first observed on 16th day of embryogenesis surrounding the developing follicle buds. Tenascin-C blocked B-cell migration in the explant cultures of embryonic BF. Similarly, RCAS-Shh retroviral vector-induced overexpression of Tenascin-C inhibits B-cell colonization of developing follicles. In summary: 1) development of the follicle cortex starts before hatching; 2) the B-cells of the cortical follicle shows a specific Bu-1+\/CXCR4+\/IgM low expression pattern, and has a CSF1R+\/TIM4+\/Lep100+ macrophage population; 3) the scaffold of the cortex is composed of mesenchymal reticulum cells that produce ECM; 4) In vivo and in vitro experiments show that Tenascin-C provides an inhibitory environment for B-cell migration. Grant: NKFI-124740<\/p>\n<\/div>\n<\/div>\n
The avian respiratory system shows unique morphological features compared to other vertebrates. Current explanations of its functional morphology suggest that it is optimized for gas exchange. The air passages start with the nasal and oral cavities, which are followed by the pharynx, larynx, trachea, syrinx, and primary bronchi. The primary bronchi enter the lungs, whereas the secondary bronchi branch from the intrapulmonary section of the primary bronchi. The organized bronchus-associated lymphoid tissue (BALT) accumulates at the opening of the distal secondary bronchi. The primary bronchus and secondary bronchi are connected to the air sacs, which are air reservoirs that function as bellows. The tertiary bronchi, or parabronchi, offshoot from the secondary bronchi. The parabronchial unit is a complex structure of air passages and gas exchange areas. The atria open from the parabronchus (PB) cavity through the discontinuous smooth muscle layer. The atrium is the main surfactant-producing area, while the funnel-shaped infundibulum is the transition between the air passage and the air capillary-blood capillary system. The actual airflow may be regulated through the atrium by the smooth muscle layer of the PB. The diffusion barrier between the air and blood capillaries is extremely thin, approximately 0.1-0.2 \u03bcm. The directions of air and blood flows are opposite, which further increases the effectiveness of avian respiration. The branches of pulmonary arteries and veins run in interparabronchial septae. The airflow is unidirectional through most of the gas-exchanging part of the avian lung (in the paleopulmo), although bidirectional air flow is also described (neopulmo).<\/p>\n<\/div>\n<\/div>\n