Meiosis is a specialized division of germ cells in sexually reproducing organisms, which is a fundamental process with key implications for evolution and biodiversity. In two consecutive rounds of cell division, meiosis I and meiosis II, a normal, diploid set of chromosome is halved. From diploid mother cells haploid gametes are generated to create genetic individual cells. This genetic uniqueness is obtained during prophase of meiosis I by essential meiotic processes in meiotic recombination, as double strand break (DSB) formation and repair, formation of crossovers (CO) and holiday junctions (HJs). Checkpoint mechanisms ensure a smooth progress of these events. Despite extensive research key mechanisms are still not understood. Based on an analysis of Massive Parallel Sequencing (MPS) data I could identify 2 genes, Mcmdc2 and Prr19, with high implication in meiotic recombination. In the absence of Mcmdc2 both sexes are infertile and meiocytes arrest at a stage equivalent to mid-­‐pachytene in wt. Investigations of the synaptonemal complex (SC) formation revealed severe defects suggesting a role for MCMDC2 in homology search. Moreover, MCMDC2 does not seem to be essential for DSB repair, as DSB markers of early and mid recombination nodules, like DMC1 and RPA, are decreased in oocytes. Nevertheless, late recombination nodules, which are positive for MutL homolog 1 (MLH1), do not form in both sexes. The absence of the asynapsis surveillance checkpoint mechanism in Hormad2 deficient ovaries with Mcmdc2 mutant background allowed survival of oocytes. This points into the direction that Mcmdc2 knock­out oocytes get eliminated after prophase I due to failed homologous synapsis. Interestingly, MCMDC2 contains a conserved helicase domain, like the MCM protein family members MCM8 and MCM9. I therefore hyphothesize that Mcmdc2 promotes homolgy search.

Die vorliegende Arbeit wurde im Rahmen einer kooperativen Promotion zwischen der TU Dresden und der Hochschule Mittweida angefertigt. In dieser werden neuartige, computerorientierte Ansätze für die Analyse von Membranproteinen vorgestellt. Membranproteine sind von essentieller Bedeutung für eine Vielzahl biologischer Prozesse innerhalb eines Organismus und stellen wichtige Zielmoleküle für eine breite Palette von Pharmazeutika dar. Ihre Sequenzen liefern wertvolle und teilweise noch nicht entschlüsselte Informationen über die dreidimensionale Struktur und funktionale Eigenschaften. Innerhalb der Proteomik und Genomik stellen Analysen an Membranproteinstrukturen einen wichtigen Teil für das Verständnis komplexer biologischer Prozesse dar. Im Zuge von Untersuchungen an Membranproteinen konnte eine Vielzahl kurzer wiederkehrender Muster, sogenannte Motive, in den Sequenzen von Membranproteinen beobachtet werden. Diese Motive unterstützen das Verständnis, wie sich Membranproteine in der Zellmembran falten. Im Fokus dieser Arbeit stehen derartige Sequenzmotive. Innerhalb von drei Projekten bilden ausschließlich sequenzmotivbasierte Ansätze die Grundlage für nähere Untersuchungen an Membranproteinstrukturen. Letztendlich liefern die in dieser Arbeit postulierten Methoden wertvolle Erkenntnisse über die strukturelle und funktionelle Rolle von Sequenzmotiven, auf deren Grundlage dazu beigetragen wird, den komplexen Aufbau von Membranproteinen besser verstehen zu können. Generell wird die Zusammenführung proteomischer und mutagener Informationen intensiviert. Nicht zuletzt wird dazu beigetragen, die in dieser Arbeit zusammengetragenen Ergebnisse, für die Planung von in vitro Experimenten sowie weiterführenden Arbeiten auf dem Gebiet der Membranproteinanalyse, der Wissenschaft zur Verfügung zu stellen. / The present work was written as part of a cooperative doctorate between the TU Dresden and the University of Applied Sciences Mittweida. In the doctoral thesis, novel, computer-oriented approaches for the analysis of membrane proteins are presented. Membrane proteins are essential for many cellular processes and are important targets for a wide range of pharmaceuticals. Their sequences provide valuable and partly not yet decoded information about their three-dimensional structure and functional characteristics. The analysis of membrane proteins is an important part for the understanding of complex biological processes in the context of proteomics and genomics. Research of membrane proteins revealed a large number of short, distinct sequence motifs. The motifs found so far support the understanding of the folded protein in the Membrane environment. In this dissertation, in three different approaches it is shown how the output of sequence motif-based methods can support the understanding of structural and functional properties of membrane proteins. In general, the junction of proteomic and mutagenic information is intensified. Last but not least, the results of this work are made available for the planning of in vitro experiments as well as for further works in the field of membrane Protein analysis.

How our career history influences experiences of our body in old age - abiography-based, mediaassisted analysis

Im Rahmen des BioPara Netzwerkes: „Gesamterfassung von biochemischen und metagenomischen Parametern in Biogasanlagen und deren Korrelation zur Produkteffizienz“ erfolgte die in dieser Arbeit durchgeführte Isolierung und Charakterisierung von prozessrelevanten methanogenen Archaeen aus frischen Schlammproben einer kommerziellen Biogasanlage. Insgesamt wurden sechs verschiedene Arten der Gattungen Methanobacterium, Methanoculleus sowie Methanosarcina isoliert und als Reinkultur kultiviert. Darunter wurden mit Methanobacterium aggregans und Methanosarcina flavescens bis dahin unbekannte Spezies identifiziert und umfassend charakterisiert. Außerdem erfolgte mit Methanoculleus bourgensis und M. flavescens die Anreicherung der beiden abundantesten methanoarchaealen Mikroorganismen des beprobten Biogasreaktors. Weiterführend wurde ein anaerobes Testsystem etabliert, um die Methanproduktivität der analysierten Biogasanlagen im Labormaßstab abzubilden. Mit diesem Testsystem wurden die hydrogenotrophen und methylotrophen Wege der Methanogenese als potentiell raten-limitierende Schritte des Biogasprozesses in NawaRo-Anlagen analysiert. Die hydrogenotrophe Methanogenese verlief in allen beprobten Biogasreaktoren nicht an der maximalen Kapazitätsgrenze und stellte daher keinen raten-limitierenden Schritt dar. Weiterführend wurde die methylotrophe Methanogenese bei hohen Methanosarcina-Abundanzen als nicht-ratenlimitierender Prozess identifiziert und durch die Zugabe von Isolat E03.2 zu inaktivierten Schlammproben der untersuchten Biogasanlagen, ergaben sich Hinweise auf die Anwesenheit von Methoxygruppen. Aufgrund der fundamentalen Bedeutung des Wasserstoff-Stoffwechsels in NawaRo-Biogasanlagen, wurden u.a. Wasserstoff-abhängige Gesamt- sowie methanoarchaeale Enzymreaktionen aus frischen Schlammproben quantifiziert und als mögliche Parameter zur Prozessüberwachung analysiert. Dabei konnte eine positive Korrelation der Gesamt-Hydrogenaseaktivität mit der Methanproduktivität in den untersuchten Biogasanlagen gezeigt werden. Die Gesamt-Hydrogenaseaktivität ist somit einen aussagekräftiger Parameter zur Prozesskontrolle.

Ectotherms are living creatures whose body temperature varies with the environment in which they live. Their physiology and metabolism have to rapidly respond to environmental changes in order to stay viable at across their tolerable thermal range (Lithgow et al. 1994). In nematodes such as Caenorhabditis elegans, temperature is an important factor that defines the fertility of the worm. A feature that delimits an ectotherm’s thermal range is the maximum temperature at which its germ line can produce gametes. How germ cells withstand high environmental stressors such as limiting temperatures is not well understood, especially when considering the thermodynamical principles that dominate the biochemical processes of the cytoplasm (Hyman and Brangwynne 2011). Previous studies in C. elegans have shown that the thermodynamic effects of temperature on the cell cycle rate in nematodes follows an Arrhenius relationship and defines the thermal range where worms can be fertile. At the limits of this relationship a breakdown of the Arrhenius trend is observed (Begasse et al. 2015a). It was hypothesized that some type of discontinuous phase transition occurred in the embryonic cells of C. elegans (Begasse et al 2015). However, it remains unknown if there is the physiological link between a drop off in fertility and the embryonic breakdown of the Arrhenius trend. This work finds the link between a temperature driven phase separation of P granules and fertility. P granules are important for germ line development and the fertility of C. elegans (Kawasaki et al. 1998b). Here it is shown that P granules mix with the cytoplasm upon a temperature quench of 27ºC to T=18ºC and de-mix from the cytoplasm forming droplets upon a temperature downshift of temperature from 18ºC to 27ºC. P granules also show a reversible behavior mixing and de-mixing with changes in temperature in vivo, having a strong dependence of these liquid-like compartments with entropy. These results were further confirmed using a minimally reconstituted, in vitro P granule system and showed that PGL-3, a constitutive component of P granules, can phase separate and form liquid compartments in a similar way as happens in vivo. Additionally, here it is shown that P granule phase separation does not require the chemical activity of other cytoplasmic factors to drive the phase separation of compartments in vivo and in vitro, instead their formation is strongly driven to mix and de-mix with changes in temperature. Furthermore, a binary phase diagram was constructed in order to compare the response of P granules in vivo and in vitro, showing that P granules form and function as a temperature driven liquid phaseseparation. Altogether, this indicates that P granules in vivo and PGL-3 liquid-like compartments in vitro, share the same temperature of mixing and de-mixing which coincides with the fertile temperature range over which Caenorhabditis elegans can reproduce. This suggests that P granule phase separation could define the thermal range of the worm.:Table of Contents 1. Abstract 2. Introduction 2 . 1 . CYTOPLASMIC ORGANIZAT ION 2 . 2 . CYTOPLASMIC PHASE SEPARATIONS 2 . 3 . P GRANULES RESEMBLE L IQUID- L IKE PROPERTI ES 2 . 4 . PHASE CHANGES AND THE CELL CYCLE 3. Aim 4. Methods 4 . 1 . STRAINS 4 . 2 . TEMPERATURE CONTROL 4.2.1. HEATING/COOLING SETUP DEVELOPMENT AND MICROSCOPE STAGE 4.2.2. CONFOCAL SAMPLE HOLDER AND HEATING/COOLING DEVICE 4.2.3. SAMPLE PREPARATION 4.2.4. TEMPERATURE OF THE MICROSCOPE OBJECTIVE 4 . 3 . IN VI VO ASSAYS 4 . 4 . IN VI TRO ASSAY 5. Results 5 . 1 . TEMPERATURE AND P GRANULE PHASE SEPARATION 5 . 2 . P GRANULES ARE TEMPERATURE SENSITIVE COMPARTMENTS 5 . 3 . P GRANULES MIX WITH THE CYTOPLASM AT 27ºC 5 . 4 . P GRANULES DO NOT NEED THE INFLUENCE OF PPTR- 1 TO FORM DROPLETS 5 . 5 . P GRANULES REVERSIBLY MIX AND DE-MIX IN VIVO 5 . 6 . PGL- 3 GRANULES PHASE SEPARATE IN V ITRO AT PHYSIOLOGICAL CONDITIONS 5 . 7 . P GRANULE PHASE SEPARATION IS REVERSIBLE IN VI VO AND IN VI TRO 5 . 8 . AN IN V ITRO PHASE DIAGRAM TO COMPARE THE THERMAL L IMITS OF P GRANULES IN V IVO 6. Discussion 6 . 1 . P GRANULES MIX AND DE-MIX IN A REVERSIBLE MANNER 6 . 2 . CONCENTRATION AND THE SPATIAL CONTROL OF P GRANULES 6 . 3 . THE ROLE OF OTHER CHEMICAL REGULATORS 6 . 4 . ECOLOGICAL RELEVANCE OF P GRANULE PHASE SEPARATION 7. Concluding Remarks 8. Bibliography

Hybride Mikroschwimmer, die einen biologischen Antrieb und eine künstlich hergestellte Mikrostruktur enthalten sind ein attraktiver Ansatz um kontrollierte Bewegung auf kleinstem Maßstab zu erreichen. In dieser Dissertation wird ein neuer hybrider Mikroschwimmer vorgestellt, der aus ferromagnetischen Nanomembranen besteht, die sich zu Mikroröhrchen aufrollen und in der Lage sind, einzelne Spermien einzufangen. Dieser Mikrobioroboter nutzt die starke Antriebskraft der Spermazelle um das magnetische Mikroröhrchen fortzubewegen. Die vorliegende Arbeit beschreibt, wie dieser Mikroschwimmer seine Bewegung vollzieht und wie verschiedene Faktoren wie Temperatur, Radius der Mikroröhrchen, Eindringtiefe der Spermien in das Röhrchen und Länge der Röhrchen einen Einfluss auf sein Verhalten haben. Richtungskontrolle wird durch externe magnetische Felder realisiert und es wird dargestellt, wie dies zur Trennung der Mikrobioroboter aus einer Mischung von Spermien und Mikroröhrchen genutzt werden kann. Weiterhin werden zwei Oberflächenmodifizierungsmethoden angewandt um die Kupplungseffizienz zwischen Mikroröhrchen und Spermien zu erhöhen. In diesen Methoden wird das extrazelluläre Protein Fibronektin auf die innere Röhrchenoberfläche aufgebracht und dient als Bindungsstoff für Spermien. Schließlich wird durch den Einbau temperatursensitiver Material in die Mikroröhrchen ein ferngesteuerter Freisetzungsmechanismus für die Spermazelle vorgestellt. Dabei falten sich die Mikroröhrchen bei kleinen Temperaturerhöhungen auf und setzen die Zelle frei. Diese Arbeit diskutiert letztendlich das Potential solch eines hybriden Mikroschwimmers für die Anwendung in assistierter Reproduktion.:TABLE OF CONTENTS SELBSTSTÄNDIGKEITSERKLÄRUNG 0 ABSTRACT 1 TABLE OF CONTENTS 3 1 MOTIVATION AND GOALS 5 1.1 MINIATURIZATION: “THERE IS PLENTY OF ROOM AT THE BOTTOM…” 5 1.2 SPERMBOTS: POTENTIAL IMPACT 7 2 BACKGROUND AND STATE-OF-THE-ART 11 2.1 MICROBIOROBOTICS 11 2.2 SPERM MORPHOLOGY AND THEIR JOURNEY TO THE EGG 15 2.3 INFERTILITY AND ASSISTED REPRODUCTION TECHNIQUES 19 2.4 SINGLE CELL RELEASE 22 2.5 STIMULI-RESPONSIVE MATERIALS 25 3 MATERIAL AND METHODS 29 3.1 ROLLED UP TECHNOLOGY 29 3.2 TREATMENT OF BOVINE SPERMATOZOA 32 3.2.1 Preparation of Spermbots 32 3.2.2 Speed Measurements 33 3.2.3 Separation On Chip 33 3.3 SURFACE MODIFICATION OF MICROTUBES 34 3.3.1 Surface Chemistry 35 3.3.2 Microcontact printing 39 3.4 POLYMER TUBE FABRICATION 44 3.4.1 Synthesis of photosensitive monomer 4-Acryloylbenzophenone 44 3.4.2 Synthesis of poly (N-isopropylacrylamide-co-Acryloylbenzophenone) 46 3.4.3 Photolithography of polymeric films 48 3.5 VIABILITY TESTS 51 4 RESULTS AND DISCUSSION 53 4.1 CHARACTERIZATION OF SPERMBOTS 55 4.2 TEMPERATURE INFLUENCE 60 4.3 MAGNETIC CONTROL 62 4.4 SEPARATION ON CHIP 68 4.5 EFFECT OF DECREASED MICROTUBE LENGTH 72 4.6 COUPLING EFFICIENCY 74 4.7 THERMORESPONSIVE POLYMERIC MICROTUBES FOR CELL RELEASE 80 4.8 SPERM VIABILITY TESTS 94 5 SUMMARY AND CONCLUSIONS 97 6 OUTLOOK 101 7 LIST OF FIGURES 107 8 LIST OF TABLES 113 9 ABBREVIATIONS 115 10 CURRICULUM VITAE 117 11 LIST OF PUBLICATIONS 119 JOURNAL ARTICLES 119 CONTRIBUTIONS TO COLLECTED EDITIONS/PROCEEDINGS 121 12 ACKNOWLEDGEMENTS 123 13 REFERENCES 125 / The search for autonomously moving, highly functional and controllable microdevices is a purpose of current micro/nanobiotechnology research, especially in the area of biomedical applications, for which reason, biocompatible solutions are in demand. In this thesis, a novel type of hybrid microswimmer is fabricated by the combination of rolled up thin nanomembranes with bovine spermatozoa. The microbiorobot presented here uses the powerful motion of the sperm flagella as a propulsion source for the magnetic microtube. This work demonstrates how the microswimmer performs its motion and how several factors such as temperature, radius of the microtube, penetration of the cell inside the microtube and length of the tube have influence on its performance. Directional control mechanisms are offered by external magnetic fields and are presented to be useful for the on-chip separation of the microbiorobots from a mixture of cells and microtubes. Two surface modification methods are presented as means to improve the coupling efficiency between the microtubes and the sperm cells. By these surface functionalizations, the extracellular matrix protein fibronectin is attached on the inner microtube walls and serves as binding agent for the spermatozoa. Finally, a remote release mechanism for the sperm cells is demonstrated by the incorporation of thermoresponsive material into the microtubes, which makes them fold and unfold upon small temperature changes. This work discusses the potential of such microswimmers for the application in assisted reproduction techniques and gives an outlook on future perspectives.:TABLE OF CONTENTS SELBSTSTÄNDIGKEITSERKLÄRUNG 0 ABSTRACT 1 TABLE OF CONTENTS 3 1 MOTIVATION AND GOALS 5 1.1 MINIATURIZATION: “THERE IS PLENTY OF ROOM AT THE BOTTOM…” 5 1.2 SPERMBOTS: POTENTIAL IMPACT 7 2 BACKGROUND AND STATE-OF-THE-ART 11 2.1 MICROBIOROBOTICS 11 2.2 SPERM MORPHOLOGY AND THEIR JOURNEY TO THE EGG 15 2.3 INFERTILITY AND ASSISTED REPRODUCTION TECHNIQUES 19 2.4 SINGLE CELL RELEASE 22 2.5 STIMULI-RESPONSIVE MATERIALS 25 3 MATERIAL AND METHODS 29 3.1 ROLLED UP TECHNOLOGY 29 3.2 TREATMENT OF BOVINE SPERMATOZOA 32 3.2.1 Preparation of Spermbots 32 3.2.2 Speed Measurements 33 3.2.3 Separation On Chip 33 3.3 SURFACE MODIFICATION OF MICROTUBES 34 3.3.1 Surface Chemistry 35 3.3.2 Microcontact printing 39 3.4 POLYMER TUBE FABRICATION 44 3.4.1 Synthesis of photosensitive monomer 4-Acryloylbenzophenone 44 3.4.2 Synthesis of poly (N-isopropylacrylamide-co-Acryloylbenzophenone) 46 3.4.3 Photolithography of polymeric films 48 3.5 VIABILITY TESTS 51 4 RESULTS AND DISCUSSION 53 4.1 CHARACTERIZATION OF SPERMBOTS 55 4.2 TEMPERATURE INFLUENCE 60 4.3 MAGNETIC CONTROL 62 4.4 SEPARATION ON CHIP 68 4.5 EFFECT OF DECREASED MICROTUBE LENGTH 72 4.6 COUPLING EFFICIENCY 74 4.7 THERMORESPONSIVE POLYMERIC MICROTUBES FOR CELL RELEASE 80 4.8 SPERM VIABILITY TESTS 94 5 SUMMARY AND CONCLUSIONS 97 6 OUTLOOK 101 7 LIST OF FIGURES 107 8 LIST OF TABLES 113 9 ABBREVIATIONS 115 10 CURRICULUM VITAE 117 11 LIST OF PUBLICATIONS 119 JOURNAL ARTICLES 119 CONTRIBUTIONS TO COLLECTED EDITIONS/PROCEEDINGS 121 12 ACKNOWLEDGEMENTS 123 13 REFERENCES 125

Stem cell niches are specialized signalling microenvironments that allow maintenance of the stem cells. According to the traditional model of the stem cell niche, the niche signalling input is integrated by a cell towards a binary decision between stemness and differentiation. I have studied the regulation of somatic cyst stem cell (CyCS) proliferation in the testicular stem cell niche of Drosophila melanogaster by performing the DamID screen for targets of the transcriptional regulator Zfh1, a shared target of Jak/STAT and Hedgehog niche signalling. I have found that Zfh1 binds to the regulatory regions of kibra and salvador, tumour suppressors of the Hippo/Yorkie pathway, and downregulates them, restricting Yorkie activity to the Zfh1 positive CySCs. Clonal inactivation of the Hippo pathway is sufficient for CySC proliferation, but does not affect their differentiation ability. I therefore proposed a different stem cell niche model, whereby the niche signalling directly “micromanage” stem cell behavior, not involving the cell fate decision making.

Under unfavorable environmental conditions Caenorhabditis elegans larvae enter a dauer stage which is a specialized non-feeding larval stage. In the dauer stage, worms display astonishingly low metabolism, which allows them to adapt themselves to environmental stress and to dwell without food for several months. Dauer larvae can enter into the reproductive larval stage, when environmental conditions become favorable. In this study, the metabolic transition of dauers into the reproductive larval stage is analyzed in detail: a. During the exit of dauers, several metabolic traits were examined. Primarily, dauer larva initiates the metabolic transition by activating feeding, which is followed by upregulated oxygen consumption and mitochondrial remodeling, as well as enhanced protein synthesis. b. To better understand the metabolic transition, inhibitors of the dauer exit were introduced. Lithium ions were shown to inhibit the transition of dauers to reproductive larvae and prevent the upregulation of metabolic activities required for this process. c. In liquid culture, the transition from the dauer to the reproductive larva is also inhibited, presumably because of the hypoxic character of the liquid culture. Thus, hypoxia has a negative effect on the metabolic transition. d. In the course of our investigation we discovered that the dauer larva is not a closed system but indeed, it can dwell on the externally available ethanol as a carbon source by incorporating it into the energy metabolism. This allows dauers to survive for longer periods in the absence of bacteria, the preferred food of worms. These findings clarify the nature of dauers, how they utilize distinct pathways during the metabolic transition and how they take advantage of the externally available carbon source. These results may in the future enable us to elucidate the complex pathways of metabolism, as well as the ways in which it can be regulated.

At the onset of cell division microtubules growing from spindle pole bodies (SPB) interact with each other to form the mitotic spindle enabling proper chromosome positioning and segregation. However, the exact mechanism of microtubule dynamics and microtubule associated proteins (MAPs) underlying spindle assembly is still not well understood. We developed an in vivo method to observe spindle assembly in the fission yeast Schizosaccharomyces pombe by inducing depolymerization of already formed and grown spindles by subjecting the cells to low temperatures, followed by subsequent repolymerization at a permissive temperature. We observed that microtubules pivot, i.e., perform angular movement around the SPB in a random manner, exploring the intranuclear space. Eventually microtubules extending from opposite SPBs come into contact and establish an antiparallel connection thus reassembling the spindle. Mutant approaches revealed that deletion of ase1 and klp5 did not prevent spindle reassembly, however introduced aberrations during the spindle formation. Amazingly, cut7p showed direct colocalization with microtubule overlap during spindle reassembly. Abrogation of cut7p led to inability to form a functional spindle. Thus, cut7p is the main regulator of spindle formation in fission yeast. None of the mutant strains affected microtubule pivoting, confirming that microtubule pivoting is a random movement unrelated to MAPs.

Developing tissues are out-of-equilibrium systems that grow and reshape to form organs in adult animals. They are typically composed of a large number of cells. The constitutive cells of a tissue perform different roles in tissue development and contribute to the overall tissue shape changes. In this thesis, we construct a hydrodynamic theory of developing epithelial tissues. We use it to investigate the developing wing of the fruit fly Drosophila melanogaster. This theory relates the coarse-grained cell scale properties to the large-scale tissue flows. We explicitly account for the active cellular processes in the tissue that drive tissue flows. In our description of the tissue, we also include the memory effects that are necessary to account for the experimental observations. These memory effects have a significant influence on the tissue rheology. Using this hydrodynamic theory we analyze shear flow in a developing fruit fly wing tissue. We find that the active cellular processes contribute to overall tissue flows and that memory effects are present in the wing tissue. We investigate consequences of these findings on the rheology of tissue shear flow. We find that the memory effects give rise to an inertial response that leads to oscillations in the tissue but it does not stem from the wing mass. Finally, we describe how the tissue rheology is affected by different boundary conditions. We then investigate the area changes during the pupal wing development and we construct a mechanosensitive model for the cell extrusion rate in the pupal wing. Analysis of cell extrusions in the context of this model also allows us to extract information about the cell division properties. Boundary connections between the wing tissue and surrounding cuticle are crucial for the proper development of the pupal wing. A dumpy mutant wing is strongly misshaped during the pupal wing morphogenesis. We use a simple model for the wing to show that the dumpy mutant wing can be described as a wild type wing with compromised boundary conditions. Finally, we analyze cell properties and tissue flows in a developing wing disc epithelium. Motivated by the observation of radially oriented active T1 transitions in the wing disc epithelium, we use the hydrodynamic theory to investigate the influence of such T1 transitions on stresses in the tissue. We show that sufficiently strong radially oriented active T1 transitions can contribute to the control of the tissue size. Results obtained in this thesis extend our understanding of the fly wing tissue rheology and the role of internal and external forces in the proper shaping of the wing epithelium. The hydrodynamic theory we use to describe the fly wing development provides a set of phenomenological parameters that characterize the tissue mechanics and can be experimentally measured. Therefore, we expect that future research will include and extend the hydrodynamic theory presented in this thesis.