PD. Dr.
Jörg Männer   
               

Phone: +49 (0)551 397032
Fax.: +49 (0)551 397043
E-Mail: 

       
Profile Research Publications
PD. Dr. Jörg Männer

 

The main research focus of the group “Cardio-Embryology” is on the embryonic development of the cardiovascular system. Our favorite research topics are:

Origin, formation and functional significance of the epicardium

The early embryonic heart of vertebrates is a tubular structure that is formed by merging of bilaterally paired areas of the splanchnic mesoderm. Its wall consists of only two different cell lineages, (1) the primitive myocardium which forms its outer epithelial wall, and (2) an endothelial cell lineage which forms its inner endocardial wall. The early embryonic heart, thus, lacks several functionally important components of the mature vertebrate heart such as the epicardium, the cardiac connective tissue and the coronary blood vessels. The embryonic progenitor cells of the epicardial mesothelium and of several other cardiac cell lineages derive from a primarily extracardiac source called the proepicardium (PE). The PE is a part of the pericardial wall near to venous pole of the embryonic heart tube. In this area, the pericardial mesothelium forms an accumulation of vesicular or villous protrusions – so called pericardial villi - whose cells are transferred across the free pericardial cavity to the opposite surface of the s-shaped heart loop. During the past 20 years, our group has carried out several studies on the development of the PE and epicardium. We have clarified the mechanism by which PE cells reach the heart in chick and Xenopus laevis embryos. In these species, PE-villi make direct contact to the opposite surface of the heart and form a secondary PE-derived tissue bridge which bridges the free pericardial cavity between the sinus venosus and the dorsal wall of the developing ventricles. PE-cells migrate along this tissue bridge towards the heart. We have developed microsurgical techniques for preventing epicardial formation in avian (chick, quail) embryos. Studies on epicardium-defective embryos have shown that the embryonic epicardium plays an important role in the growth of the outer compact layer of the ventricular myocardium. We have developed a microsurgical technique for orthotopic transplantation of the PE from a quail donor into a chick host (quail-chick chimeras). This technique facilitates the production of chimeric hearts in which the derivatives of the PE and embryonic epicardium are almost completely of donor origin. We have used such quail-chick chimeras for PE cell lineage analyses. Our data show that (1) PE-derived mesothelial cells form the epicardium of the whole heart while the epicardium of the great arterial trunks does not derive from the PE. (2) PE- or epicardium-derived mesenchymal cells colonize the subepicardial, myocardial and subendocardial layers including the atrio-ventricular endocardial cushions. (3) PE- or epicardium-derived mesenchymal cells provide the endothelium and smooth muscle cells of the coronary blood vessels and the majority of cardiac fibroblasts. (4) PE- or epicardium-derived mesenchymal cells do not provide a substantial number of myocardial cells. (5) PE- or epicardium-derived mesenchymal cells are only transitorily present in the atrio-ventricular endocardial cushions. They disappear from this site during advanced stages of development, and do not substantially contribute to the formation of the mature atrio-ventricular valves. (6) PE- or epicardium-derived mesenchymal cells do not substantially contribute to the endothelium of the cardiac lymphatic vessels. We have documented the existence of bilaterally paired PE-anlagen in chick and mouse embryos. Our studies disclosed interesting species-specific differences in the morphogenesis of these paired PE-anlagen. In mouse embryos, the two PE-anlagen grow in a bilaterally symmetric pattern, so that both PE-anlagen contribute to the mature PE. In chick embryos, on the other hand, only the right PE-anlage grows and forms the mature PE while the left PE-anlage undergoes apoptosis. An asymmetric, right-sided formation of the PE was also documented in Xenopus laevis. Our findings suggest that, in avian and amphibian embryos, PE development might be controlled by signals involved in the specification of the left-right body axis (see below). Several projects on PE development were carried out in collaboration with Prof. Dr. Thomas Brand (Chair in Developmental Dynamics, Heart Science Centre, Cardiovascular Sciences/NHLI, Faculty of Medicine, Imperial College London).

References

  • Jahr M, Schlueter J, Brand T, Männer J, (2008) Development of the proepicardium in Xenopus laevis. Dev Dyn 233:1454-1463.
  • Norozi K, Thrane L, Männer J, Pedersen F, Wolf I, Mottl-Link S, Meinzer HP, Wessel A, Yelbuz TM. (2008) In vivo visualization of coronary artery development by high-resolution optical coherence topmography. Heart 94:130.
  • Männer J, Ruiz-Lozano P. (2007) Development and function of the epicardium. Adv Dev Biol. 18:333-357. Review.
  • Zamora M, Männer J, Ruiz-Lozano P. (2007) Epicardium-derived progenitor cells require ß-catenin for coronary artery formation. PNAS 104:18109-18114.
  • Wilting J, Buttler K, Schulte I, Papoutsi M, Schweigerer L, Männer J, (2007) The proepicardium delivers hemangioblasts but not lymphangioblasts to the developing heart. Dev Biol 305: 451-459.
  • Schulte I, Schlueter J, Abu-Issa R, Brand T, Männer J, (2007) Morphological and molecular left-right asymmetries in the development of the proepicardium: a comparative analysis on mouse and chick embryos. Dev Dyn 236:684-695.
  • Männer J. (2006) Extracardiac tissues and the epigenetic control of myocardial development in vertebrate embryos. Ann Anat. 188:199-212. Review.
    Schlueter J, Männer J, Brand T. (2006) BMP is an important regulator of proepicardial identity in the chick embryo. Dev Biol 295:546-558.
  • Männer J, Schlueter J, Brand T. (2005) Experimental analyses of the function of the proepicardium using a new microsurgical procedure to induce loss-of-proepicardial function in chick embryos. Dev Dyn 233:1454-1463.
  • De Lange FJ, Moorman AF, Anderson RH, Männer J, Soufan AT, de Gier-de Vries C, Schneider MD, Webb S, van den Hoff MJ, Christoffels VM. (2004) Lineage and morphogenetic analysis of the cardiac valves. Circ Res 95:645-654.
  • Männer J, Pérez-Pomarez JM, Macías D, Muñoz-Chápuli R. (2001) The origin, formation, and developmental significance of the epicardium: a review. Cells Tissues Organs 169:89-103. Review
  • Männer J. (2000) Embryology of congenital ventriculo-coronary communications: a study on quail-chick chimeras. Cardiol Young 10: 233-238.
    Männer J. (1999) Does the subepicardial mesenchyme contribute myocardioblasts to the myocardium of the chick embryo heart? A quail-chick chimera study tracing the fate of the epicardial primordium. Anat Rec 255: 212-226.
  • Männer J. (1998) The origin and course of coronary vessels: embryological considerations. Cardiol Young 8: 534-535.
  • Männer J. (1993) Experimental study on the formation of the epicardium in chick embryos. Anat Embryol 187: 281-289.
  • Männer J. (1992) The development of pericardial villi in the chick embryo. Anat Embryol 186: 379-385.

 

Morphogenesis of visceral left-right asymmetries 1: Breaking the bilateral symmetry of early vertebrate embryos

The internal organs of vertebrates show species-specific left-right (L-R) asymmetries. The question of how these asymmetries arise from the initially bilateral symmetry of early vertebrate embryos has been fascinating embryologists and anatomists since the 19th century. This question is also of special interest to Cardio-Embryology since the function of the mature cardiovascular system is highly dependent on asymmetric morphogenesis of the heart and blood vessels. Furthermore, the embryonic heart is the first organ to develop overt topographical and morphological L-R asymmetries (see Cardiac looping) and is, therefore, frequently used as a morphological indicator for body sidedness in experimental studies on early vertebrate embryos. During the past few years, molecular signaling cascades have been identified that control the acquisition of the left and right identities of the embryonic body halves. These signaling cascades start from Hensen’s node. It is, however, a matter of debate what initiates these signaling cascades. In mouse embryos, the fluid flow caused by the rotatory movement of monocilia located at the ventral surface of the node (so-called “ventral node“) is said to initiate the L-R signaling cascades (nodal flow hypothesis). Corresponding ciliated structures have been identified in rabbit, zebrafish (Kupfer’s vesicle) and Xenopus laevis (gastrocoel roof plate) embryos. In chick embryos, however, we could not find an equivalent ciliated structure, suggesting that “nodal flow“ does not initiate the L-R signaling cascades in avian embryos.

References

  • Dathe V, Gamel A, Männer J, Brand-Saberi B, Christ B (2002) Morphological left-right asymmetry of Hensen's node precedes the asymmetric expression of Shh and Fgf8 in the chick embryo. Anat Embryol 205:343-354.
  • Männer J (2001) Does an equivalent of the "ventral node" exist in chick embryos? A scanning electron microscopic study. Anat Embryol 203: 481-490.

 

Morphogenesis of visceral left-right asymmetries 2: Cardiac looping

The vertebrate heart arises from the merging of corresponding areas of the left and right splanchnic mesoderms ventral to the developing foregut. During the initial phase of its establishment, the embryonic heart appears as a straight and bilaterally almost symmetric tube oriented along the ventral midline of the foregut (cranio-caudal axis). This tubular heart consists only of the primordia of the apical trabeculated regions of the future ventricular chambers. It is connected to the developing veins at its caudal end (venous pole) and to the developing arteries at its cranial end (arterial pole). Subsequent to its establishment, the initially short heart tube becomes elongated by the continuous addition of new cardiac segments (atrio-ventricular canal, common atrium, sinus venosus, outflow tract) to its venous and arterial ends. The elongation of the embryonic heart tube is accompanied by the transformation of its initially straight configuration into a convoluted heart loop. This process is usually named “cardiac looping”. It is generally stated that cardiac looping brings the subdivisions of the heart tube and the main stems of the blood vessels into an approximation of their definitive topographical relationships to each other. This is especially important for the positioning of the ventricular chambers. The future left and right ventricular chambers are originally aligned along the cranio-caudal body axis. They are both formed by material from the left as well as right splanchnic mesoderms. The emergence of their morphological identities, which are characterized by different patterns of myocardial trabeculation, is not linked to the specification of the L-R body axis but is linked to the specification of the cranio-caudal heart axis. It is the looping process that transforms the original cranio-caudal topology of the ventricular chambers into the L-R topology seen in the mature four-chambered heart. In view of its key role in the morphogenesis of the heart, especially in the positioning of the ventricular chambers, the elucidation of the factors that drive cardiac looping is of fundamental interest not only to understand the normal morphogenesis of the embryonic heart but also to understand the morphogenesis of congenital cardiac malformations. During the first phase of cardiac looping, the initially straight heart tube becomes transformed into a so-called “c-shaped” heart loop, which is usually regarded as the first visible manifestation of visceral L-R asymmetries. The curved portion of the c-shaped heart loop consists of the future ventricular chambers and, therefore, is frequently named the “ventricular loop”. Its convexity normally points towards the right side of the body in all vertebrate species. Hence, the normal heart loop is traditionally classified as a right-handed loop or dextral-loop (D-loop). Mirror-imaged heart loops with a convexity pointing towards the left side of the body can occur but are exceedingly rare findings. Such loops were traditionally classified as left-handed loops or levo-loops (L-loop). The developmental “plan” of the vertebrate heart obviously favors one of two possible geometric configurations. Since the 19th century, scientists were fascinated by the fact that the developing vertebrate heart almost always loops towards the right side of the body. Studies on looping morphogenesis of the heart, therefore, have almost exclusively focused on the problem of the determination of the direction of heart looping. It was not before the end of the 20th century, however, when developmental biologists uncovered that the direction of heart looping is linked to phylogenetically highly conserved L-R signaling pathways. The genetic basis of L-R axis specification may explain the dominance of dextral-looping among vertebrate species. It is still an open question, however, how the molecular L-R signals are physically translated into looping morphogenesis. The main goal of our research on dextral-looping is to identify biophysical processes that drive the morphological and topographical changes of the looping heart tube. Our studies have shown that dextral-looping is not simply a bending of the straight heart tube towards the right side of the body, as it has frequently been misinterpreted. Dextral-looping results mainly from two different morphogenetic processes (1) bending of the ventricular region of the straight heart tube towards its original ventral side, and (2) rotation of the ventricular loop around the dorsal mesocardium so that its original ventral side finally forms the right convex curvature of the c-shaped heart. We have additionally shown that the rotation of the heart loop around its dorsal mesocardium does not only lead to the lateral displacement of its ventricular loop either towards the right (D-loop) or left (L-loop) side of the embryo. A further consequence is torsion of the ventricular loop into a helical structure that is wound either clockwise (right-handed helix) or counterclockwise (left-handed helix). Interestingly, normal heart loops present as D-loops with left-handed helical winding while their mirror images present as L-loops with right-handed helical winding. This conflict with the use to define D-loops as right-handed and L-loops as left-handed structures. Moreover, we have shown that the traditional approach to classify the L-R asymmetry of the embryonic heart simply in terms of D- and L-loop does not properly define the morphological asymmetry of the heart loop but simply define its position with respect to the body midline. Defining the morphology of the heart loop simply in terms of D- and L-loop may lead to misinterpretations of experimental results. The process of dextral-/levo-looping determines the basic type of topological L-R asymmetry of the future ventricular chambers and, therefore, receives considerable attention from those developmental biologists researching on the specification of the L-R body axis. It should be noted, however, that at the end of dextral-/levo-looping, the future ventricular chambers are still in an immature position cranial to the developing atriums. Since cardiac looping is said to bring the subdivisions of the heart tube and the main stems of the blood vessels into an approximation of their definitive topographical relationships to each other (see above), dextral-/levo-looping cannot be regarded as the whole story of cardiac looping. Therefore, our research on cardiac morphogenesis does not only focus on dextral-/levo-looping. We also want to identify those morphogenetic processes that transform the c-shaped heart loop into a configuration, which is usually described as the “s-shaped” heart loop. We distinguish between an early and a late s-looping phase. The early phase of s-looping is mainly characterized by (1) displacement of the ventricular loop from its original position cranial to the atriums towards its final position caudal to the atriums; and (2) shortening of the distance between the fixed arterial and venous poles of the heart. Our experimental studies on chick embryos have shown that the shortening of the distance between the arterial and venous poles and the caudal displacement of the ventricular loop are both related to the formation of the cervical flexure of the embryo. The late s-looping phase is mainly characterized by (1) ventral shift of the primitive right ventricle; (2) ventral and rightward shift of the proximal portion of the cardiac outflow tract; and (3) leftward shift of the atrio-ventricular canal. In order to identify the morphogenetic processes driving the late s-looping phase, we have developed an animal (chick) model for a complex congenital heart defect with “double-outlet right ventricle” in combination with “left juxtaposition of the atrial appendages”. The topographical situation found in this heart defect resembles that of embryonic heart loops at the end of the early s-looping phase suggesting that it may be the consequence of defective late s-looping morphogenesis.

References

  • Männer J. (2009) The anatomy of cardiac looping: a step towards the understanding of the morphogenesis of several forms of congenital cardiac malformations. Clin Anat 22:21-35. Review.
  • Männer J. (2006) Ontogenetic development of the helical heart: concepts and facts. Eur J Cardiothorac Surg. 29 (Suppl 1):S69-74. Review.
  • Männer J. (2004) On rotation, torsion, lateralization, and handedness of the embryonic heart loop: new insights from a simulation model for the heart loop of chick embryos. Anat Rec 278A: 481-492.
  • Männer J, Heinicke F (2003) A model for left juxtaposition of the atrial appendages in the chick. Cardiol Young 13:152-160.
  • Männer J. (2000) Cardiac looping in the chick embryo: a morphological review with special reference to terminological and biomechanical aspects of the looping process. Anat Rec 259: 248-262. Review.
  • Männer J, Seidl W, Steding G. (1996) Experimental study on the significance of abnormal cardiac looping for the development of cardiovascular anomalies in neural crest-ablated chick embryos. Anat Embryol 194: 289-300.
  • Männer J, Seidl W, Steding G. (1995) The role of extracardiac factors in normal and abnormal development of the chick embryo heart: cranial flexure and ventral thoracic wall. Anat Embryol 191: 61-72.
  • Männer J, Seidl W, Steding G. (1995) Formation of the cervical flexure: an experimental study on chick embryos. Acta Anat 152: 1-10.
  • Männer J, Seidl W, Steding G. (1993) Correlation between the embryonic head flexures and cardiac development. An experimental study in chick embryos. Anat Embryol 188: 269-285.

 

Morphogenesis of visceral left-right asymmetries 3: Development of the venous heart pole

The venous pole (atriums + great veins) of the mature heart of lung-breathing vertebrates normally shows several morphological asymmetries with respect to the L-R body axis. These are (1) striking differences in the shapes of the appendages of the right and left atriums; (2) asymmetric placement of the sinus node to the morphologically right atrium, only; and (3) asymmetric arrangement of the veno-atrial connections (systemic venous tributaries are connected to the morphologically right atrium while the pulmonary venous tributaries are connected to the morphologically left atrium). The morphologically right atrium normally is derived from the right splanchnic mesoderm while the morphologically left atrium normally is derived from the left splanchnic mesoderm. This suggests that the development of morphological L-R asymmetries at the venous heart pole might be mechanistically linked to the molecular specification of the L-R body axis. This idea is in accord with the fact that human congenital cardiac malformations with bilaterally symmetric arrangement of the atrial appendages (right or left atrial isomerism) are frequently associated with abnormal veno-atrial connections (e.g. total anomalous pulmonary venous return). However, the ways by which the atrial L-R asymmetries evolve from the originally symmetrically arranged embryonic venous heart pole are poorly defined at the present time. In this project, we want to clarify if and how the morphogenesis of the venous heart pole is mechanistically linked to the specification of the L-R body axis. Our studies focus on two structures at the venous heart pole (1) the proepicardium (see above), and (2) the common pulmonary vein. We have shown that vertebrate embryos form bilaterally paired PE-anlagen which grow in a bilaterally symmetric pattern in some species (e.g. mouse) while in others (e.g. chicks, Xenopus laevis) they grow in a unilateral right-sided pattern, suggesting that, in some species, PE development may be controlled by left or right-sided signals. Experimental data from the lab of Thomas Brand (Imperial College London) have shown that, in chick embryos, the growth of the PE is indeed controlled by right-sided signals. Due to the limited survival time of cultured chick embryos, however, experimental studies on a more suitable model organism are needed to further characterize the signals involved in asymmetric PE development. Our current studies on asymmetric PE development, therefore, focus on Xenopus laevis. With respect to the establishment of the veno-atrial connections, we have shown that, in some species (chick, Xenopus laevis), the mouth of the common pulmonary vein normally derives from the left body half and opens from the time point of its first appearance into the future left atrium. This suggests that left-sided signals may be responsible for the connection of the pulmonary venous tributaries to the developing atriums. Due to the limited survival time of cultured chick embryos, our current studies on pulmonary vein development focus on Xenopus laevis.

References

  • Jahr M, Männer J. (2011) Development of the venous pole of the heart in the frog Xenopus laevis: A morphological study with special focus on the development of the venoatrial connections. Dev Dyn. 240:1518-1527.
  • Jahr M, Schlueter J, Brand T, Männer J, (2008) Development of the proepicardium in Xenopus laevis. Dev Dyn 233:1454-1463.
  • Männer J, Merkel N. (2007) Early morphogenesis of the sinuatrial region of the chick heart: a contribution to the understanding of the pathogenesis of direct pulmonary venous connections to the right atrium and atrial septal defects in hearts with right isomerism of the atrial appendages. Anat Rec. 290:168-180.
  • Schulte I, Schlueter J, Abu-Issa R, Brand T, Männer J, (2007) Morphological and molecular left-right asymmetries in the development of the proepicardium: a comparative analysis on mouse and chick embryos. Dev Dyn 236:684-695.

 

In vivo visualization of the solid (morphological) dynamics of the pumping action of the tubular embryonic heart

The heart is the first organ to function in vertebrate embryos. In human embryos, for example, the heart starts beating around the 21st day of development (post conceptionem). During the initial phase of its pumping action, the vertebrate embryonic heart is seen as a tubular structure that is built up by (1) an inner endothelial tube lacking valves, (2) a middle layer of extracellular matrix (cardiac jelly), and (3) an outer myocardial tube. This multilayered tubular pump generates hemodynamically effective unidirectional blood flow without valves. This fact poses the question how it works. Visual examinations of the beating embryonic heart tube show that its pumping action is characterized by traveling mechanical waves sweeping from its venous to its arterial end. These waves were traditionally interpreted as myocardial peristaltic waves, suggesting that the embryonic heart tube works as a peristaltic pump. Recent in vivo data from chick and zebrafish embryos, however, suggest that the embryonic heart tube does not work as a peristaltic pump. The data rather suggest that its pumping function might be based on the so-called “Liebau-effect”. A critical evaluation of all of the currently available data has shown that the embryonic heart tube works neither as a technical peristaltic pump nor as a Liebau-effect pump. Thus, it is an open question which physical mechanism might drive the pumping action of the valveless embryonic heart tube. To answer this question, information is needed not only about the fluid dynamics but also about the solid (morphological) dynamics of the beating embryonic heart tube. In this project, we document the morphological dynamics of the valveless embryonic heart tube in living chick embryos and thereby want to contribute to the elucidation of the pumping mechanism of the early embryonic heart. This project is carried out by a multi-disciplinary team of experts consisting of Prof. Dr. med. Mesud Yelbuz (Director, Cardiovascular Development Research Laboratory) and Dr. med. Christoph M. Happel, PhD (Pediatric Cardiology Fellow) in the Dept. of Pediatric Cardiology & Intensive Care Medicine at Hannover Medical School with expertise in Pediatric Cardiology; Prof. Dr.-Ing. Tobias Ortmaier (Director, Institute of Mechatronic Systems) and Dipl.-Ing. Jan Thommes (Research Associate) at Leibniz University Hannover with expertise in imaging and image processing; Dr. Lars Thrane (Senior Scientist, DTU Fotonik, Dept. of Photonics Engineering) at Technical University of Denmark with expertise in OCT; and our group with expertise in developmental morphology. Our team uses optical coherence tomography (OCT) for non-destructive visualization of the internal and external morphology of the beating embryonic heart at high resolutions. Since the performance of the embryonic cardiovascular system is severely compromised by non-physiological environmental conditions (e.g. low temperature), our OCT examinations of embryonic chick hearts are carried out in an examination incubator, which provides stable physiological conditions.

References

  • Happel CM, Thrane L, Thommes J, Männer J, Yelbuz TM. (2011) Integration of an optical coherence tomography (OCT) system into an examination incubator to facilitate in vivo imaging of cardiovascular development in higher vertebrate embryos under stable physiological conditions. Ann Anat. 193:425-435.
  • Männer J, Wessel A, Yelbuz TM. (2010) How does the tubular embryonic heart work? Looking for the physical mechanism generating unidirectional blood flow in the valveless embryonic heart tube. Dev Dyn. 239:1035-1046. Review.
  • Männer J, Thrane L, Norozi K, Yelbuz TM. (2009) In vivo imaging of the cyclic changes in cross-sectional shape of the ventricular segment of pulsating embryonic chick hearts at stages 14 to 17: a contribution to the understanding of the ontogenesis of cardiac pumping function. Dev Dyn. 238:3273-3284.
  • Männer J, Thrane L, Norozi K, Yelbuz TM. (2008) High-resolution in vivo imaging of the cross-sectional deformations of contracting embryonic heart loops using optical coherence tomography. Dev Dyn. 237:953-961.

 

Visualization of the morphogenesis of congenital malformations in animal models for human congenital malformations (complex heart defects, facial malformations, cloacal exstrophy)

During the past decades, remarkable progress has been made in elucidating the molecular background of several types of human congenital malformations. In contrast, the morphogenesis of most congenital malformations, - that means the developmental sequence of abnormal morphological changes leading to the definitive morphological phenotype of a given malformation -, has remained an obscure matter. The reasons for this were (1) the lack of collections of human embryos and fetuses showing a given malformation at successive stages of development; (2) the lack of appropriate animal models; and (3) the lack of non-destructive, ¬imaging techniques facilitating the continuous in vivo visualization of individual embryos at a high temporal and spatial resolution under stable physiological conditions over the whole period of organogenesis. During the past few years, we have developed animal (chick) models for several human congenital malformations (median facial clefts of the type of frontonasal dysplasia, complex heart defects with left juxtaposition of the atrial appendages, cloacal exstrophy) by use of teratogens (Suramin, Trypan blue). Projects to visualize the morphogenesis of these malformations are currently being conducted by a multi-disciplinary team consisting of Prof. Dr. med. Mesud Yelbuz (Director, Cardiovascular Development Research Laboratory) and Dr. med. Christoph M. Happel, PhD (Pediatric Cardiology Fellow) in the Dept. of Pediatric Cardiology & Intensive Care Medicine at Hannover Medical School with expertise in Pediatric Cardiology; Prof. Dr.-Ing. habil. Dr.-Ing. E.h. Dr. h.c. Friedrich-Wilhelm Bach (Director, Institute of Material Sciences), Dipl.-Ing. Christian Klose (Section Head Biomedical Engineering and Lightweight Construction) with expertise in micro-CT; Prof. Dr.-Ing. Tobias Ortmaier (Director, Institute of Mechatronic Systems) and Dipl.-Ing. Jan Thommes (Research Associate) at Leibniz University Hannover with expertise in imaging and image processing; Dr. Lars Thrane (Senior Scientist, DTU Fotonik, Dept. of Photonics Engineering) at Technical University of Denmark with expertise in OCT; and our group with expertise in developmental morphology. We use new non-destructive imaging techniques (micro-computed tomography (micro-CT), optical coherence tomography (OCT)) suitable for the visualization of the internal and external morphology of small biological objects at high resolutions. Long-term in vivo examinations of chick embryos under stable environmental conditions are facilitated by the use of an examination incubator which has been developed by Prof. Dr. med. Mesud Yelbuz in collaboration with experts from the Institute of Mechatronic Systems at Leibniz University of Hannover.

References

  • Happel CM, Thrane L, Thommes J, Männer J, Yelbuz TM. (2011) Integration of an optical coherence tomography (OCT) system into an examination incubator to facilitate in vivo imaging of cardiovascular development in higher vertebrate embryos under stable physiological conditions. Ann Anat. 193:425-435.
  • Happel CM, Klose C, Witton G, Angrisani GL, Wienecke S, Groos S, Bach FW, Bormann D, Männer J, Yelbuz TM. (2010) Non-destructive, high-resolution 3-dimensional visualization of a cardiac defect in the chick embryo resembling complex heart defect in humans using micro-computed tomography: double outlet right ventricle with left juxtaposition of atrial appendages. Circulation. 122:e561-564.
  • Orhan G, Baron S, Norozi K, Männer J, Hornung O, Blume H, Misske J, Heimann B, Wessel A, Yelbuz TM. (2007) Construction and establishment of a new environmental chamber to study real-time cardiac development. Microsc Microanal. 13:204-210.
  • Männer J, Kluth D. (2005) The morphogenesis of the exstrophy-epispadias complex: a new concept based on observations made in early embryonic cases of cloacal exstrophy. Anat Embryol 210:51-57.
  • Männer J, Kluth D (2003) A chicken model to study the embryology of cloacal exstrophy. J Pediatr Surg 38:678-681.
  • Männer J, Heinicke F (2003) A model for left juxtaposition of the atrial appendages in the chick. Cardiol Young 13:152-160.
  • Männer J, Seidl W, Heinicke F, Hesse H (2003) Teratogenic effects of suramin on the chick embryo. Anat Embryol 206: 229-237.