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.

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.

Obesity is characterized by the accumulation of adipose tissue (AT) either in the major adipose depots, the subcutaneous (SAT) or visceral (VAT), or ectopically in other tissues and organs such as muscle or liver. Indeed, AT is more than just a big energy storage filled with lipids or an isolation layer for inner organs. Since the first AT-secreted components were discovered the general thinking about AT changed fundamentally. Today, AT is regarded as the largest endocrine organ that releases bioactive compounds named adipokines which fulfill a variety of biological functions ranging from the orchestration of hunger and satiety to the modulation of immune responses or inflammation. Obesity is almost always accompanied by noncommunicable diseases like diabetes mellitus, cardiovascular diseases or several types of cancer. Globally, more than 70 % of prematurely deaths are caused by noncommunicable diseases. So far, the mechanisms how obesity contributes to or causes these diseases are not fully understood. However, most patients with obesity suffer from symptoms of AT dysfunction as result of adipocyte hypertrophy, hypoxia, fibrosis or immune cell infiltration. Finally, obesity is linked to altered adipokine secretion which together with circulating free fatty acids (FFA) contribute to chronic AT inflammation which is believed to be a link between obesity and diseases. However, obesity is very heterogeneous, and about 20 % of all people with obesity are classified as metabolically healthy. In this context, body shape and therefore the distribution of AT within the body is of immense importance. This may also be explained by adipokine secretion patterns, as patients with more prominent subcutaneous obesity are more likely to be metabolically healthy than patients with predominant visceral AT accumulations. Therefore, it is of enormous scientific and public interest to comprehend genetic mechanisms regulating AT development and distribution, but also to better understand the concept of healthy and unhealthy obesity for a targeted obesity therapy or prevention. In chapter 1, I aimed to investigate the impact of Homeobox C9 (Hoxc9) gene knockout on AT development and distribution. Initially, Hoxc9 was determined as interesting candidate gene, because it was found twice as high expressed in subcutaneous than in visceral AT. Therefore, mice with an expected deletion of Hoxc9 in AT (ATHoxc9-/-) were generated by crossing floxed Hoxc9lox/lox with fatty acid-binding protein 4 (Fabp4)-Cre recombinase expressing mice. The study was driven by the hypothesis, that adipocyte-specific loss of Hoxc9 will result in impaired AT development or an imbalanced inguinal WAT (ingWAT) to epigonadal WAT (eWAT) ratio compared to littermate controls. Furthermore, ATHoxc9-/- mice were expected to be a potential model mimicking unhealthy obesity, due to potential smaller ingWAT vs. eWAT depots, finally contributing to a better understanding how obesity is linked to noncommunicable diseases. Mice of both sexes were included in the study and either fed a standard chow diet (CD) or a calorie-dense high-fat diet (HFD), to promote diet-induced obesity (DIO). Whereas female knockout mice did not show phenotypic abnormalities, repeated body weight measurements revealed lower weight gain for male ATHoxc9-/- mice under HFD. Additionally, the HFD fed ATHoxc9-/- mice exhibited better glucose tolerance, whereas also ATHoxc9-/- mice on CD had lower fasting glucose levels compared to littermates. Regarding the adipocyte size, ATHoxc9-/- mice are characterized by smaller adipocytes of both subcutaneous and visceral origin, whereas HFD lead to slightly enlarged eWAT adipocytes. In line with the leaner phenotype and better glucose tolerance, OLINK serum protein analyzes detected lower levels of inflammatory markers (e.g., Ccl5, Il17a or Il17f) in ATHoxc9-/- mice. However, analyzing the knockout efficiency revealed only minor, but not significant tendency of Hoxc9 reductions in AT on both, mRNA and protein level. Additionally, DNA fragments within the targeted Hoxc9 exon regions were still detectable in both ATHoxc9-/- and littermates. Based on this, I wanted to clarify whether the Fabp4-Cre model is adequate to induce an AT-specific knockout in genes expressed as early as Hoxc9. Therefore, I investigated several in vitro and ex vivo models. First, I cultured and differentiated three different adipocyte cell lines (3T3-L1, immortalized inguinal and epigonadal white adipocytes and SVF cells isolated from mouse AT depots) to investigate gene expression patterns of both Hoxc9 and Fabp4 from undifferentiated and mature adipocytes, as well as during differentiation. In all models, Hoxc9 was already expressed early in the undifferentiated stages, whereas Fabp4 expression started later during adipocyte maturation. Additionally, to translate these findings in vivo, I sacrificed pups within their first 20 days of age and dissected developing ingWAT depots. Measurements of Hoxc9 and Fabp4 gene and protein levels supported the previous in vitro results. Therefore, I conclude that the Fabp4 mediated Cre recombinase is not suited for the investigation of a gene’s role in adipose tissue development. Furthermore, this finding should be transferable in the context of developmental research in other tissues or organs. Accordingly, I strongly encourage researchers who wants to perform Cre-mediated gene knockouts to check expression patterns of both, the Cre-mediating gene and the gene of interest in appropriate cell models beforehand to save time and costs, but most importantly to focus on animal welfare. In addition, the missing control group of Fabp4-Cre mice may represent a second major limitation of the study. Several previous studies have reported phenotypes resulting from Cre expression alone. Therefore, and because the presence of the Fabp4-Cre recombinase was the only validated genetic difference between our ATHoxc9-/- (Hoxc9lox/lox, Fabp4-Cre+) and the littermate controls (Hoxc9lox/lox, Fabp4-Cre-), I concluded that the phenotypic differences observed between both groups resulted from the Fabp4-Cre genotype itself. Even while Hoxc9 was found to be expressed in earlier stages of adipogenesis than Fabp4, it was surprising and unexpected that Cre recombinase expression did not ablate Hoxc9 in mature adipocytes. The detection of potential expression differences was impeded by the overall low expression of Hoxc9 in AT, even if it was found differentially expressed between ingWAT and eWAT. To investigate the Hoxc9 impact on adipogenesis other Cre models mediated by promotors active during earlier stages of adipocyte differentiation should be used. Alternative adipocyte-specific Cre expressing mouse lines using the adiponectin (Adipoq) promotor or the less known resistin (Retn) promotor can be excluded for Hoxc9 as they are most active only in fully mature adipocytes. In contrast, platelet derived growth factor receptor α (Pdgfra) promotor controlled Cre expression is already active during the adipocyte progenitor stage and could be better suited to target Hoxc9. Yet, this Cre model accompanies with other pitfalls. In line with its expression in progenitor cells, the Hoxc9 gene will not just be deleted in cells with adipogenic fate, but also in progenitors developing into e.g., chondrocytes or osteoblasts. According to Hoxc9’s role in skeletal patterning during the embryogenesis, using this model may result in malformations or premature death. Finally, the paired related homeobox 1 (Prrx1) Cre line is a likely suitable model . This promotor was found to be active early in progenitor cells later found in ingWAT depots and may be suitable to investigate the role of Hoxc9 in AT development and distribution.:Table of contents 1 1. Introduction 2 Obesity – a Global Pandemic 2 The Human Adipose Tissue 2 Obesity and Dysfunction of Adipose Tissue 4 Society, Environment and Genetics in the Pathogenesis of Obesity and AT Distribution 6 Rationale for Chapter 1 8 The Developmental Control Genes of the Homeobox Family 8 Aim of the Study in Chapter 1 11 Rationale for Chapter 2 11 Adenylyl Cyclases 12 How Adenylyl Cyclases Impact Diabetes 14 Aim of the Study in Chapter 2 16 The Cre-loxP System and Generation Knockout Mouse Models 17 2. Chapter 1 19 3. Chapter 2 38 4. Summary 60 5. References 65 6. Appendix 75 A. Supplementary Material - Chapter 1 75 B. Supplementary Material - Chapter 2 82 Erklärung über die eigenständige Abfassung der Arbeit 95 Curriculum Vitae 96 List of Publications and Talks 97 Danksagung 99 / In chapter 2, I investigated the consequences of a whole-body ablation of adenylyl cyclase 5 (Adcy5) in mice. Genome-wide association studies (GWAS) identified human ADCY5 as a candidate for diabetes associated traits and a higher risk to develop type 2 diabetes (T2D). In several mouse models the loss of Adcy5 was described as beneficial. For instance, Adcy5-/- mice have shown improved cardiac function and an increased longevity, mimicking a phenotype resulting from caloric restriction. Furthermore, they were protected against DIO and did not develop glucose intolerance or insulin resistance. Therefore, my study focused on the AT phenotype and global AT gene expression profiles resulting from the whole-body loss of Adcy5. Again, I comprehensively investigated animals of both sexes, both under CD or HFD. Unexpectedly, our mice readily developed DIO. Moreover, female mice under HFD developed more severe obesity compared to control animals. Female C57BL/6 mice are in general not as susceptible to DIO as males from the same strain and usually develop later-onset and less severe obesity. Therefore, it was surprising that the loss of Adcy5 induced DIO-development in females, an effect known from ovariectomized mice. Since Adcy5 is highly expressed in the ovaries and the expression of the key enzyme of estrogen production, aromatase, is regulated by Adcy-generated cyclic adenosine monophosphate (cAMP), further studies are necessary to validate the hypothesis, that Adcy5 may affect DIO-susceptibility via the cAMP-aromatase-estrogen axis. Besides, our model did not reproduce the beneficial effects on energy expenditure, oxygen consumption or insulin sensitivity described by others. Our phenotype is more similar and matches to those described for Adcy3 deficient mice, where knockouts gained more weight under HFD than littermate controls. Again, a shortcoming of our study was not using littermate controls. Knockouts were generated by integrating a vector cassette into Adcy5 exon 1 of C57BL/6NTac mice. Mice of the same strain sharing more than 99% background identity were used as controls. However, this could explain the phenotype differences seen in our compared to earlier reported Adcy5 knockout models. Nevertheless, our model enabled us to investigate the impact of Adcy5 on AT morphology and gene expression independently of body weight or a metabolically healthier phenotype. Except for the female mice on HFD, all Adcy5 deficient mice exhibited an increased number of smaller adipocytes which is strongly correlated to a reduced diabetes risk by retaining insulin sensitivity. Conspicuously, all Adcy5-/- mice presented a tremendously reduced running wheel activity. Beside several genes of glucose and lipid metabolism, global gene expression analysis within AT highlighted sodium-potassium ATPase catalytic subunit alpha-3 (Atp1a3) as significantly higher expressed in Adcy5-/- mice. Mutations within Atp1a3 are known to be related to e.g., dyskinesia and could be a relevant finding to understand how the loss of Adcy5 is connected to movement disorders. Based on GWAS and other earlier studies in mice that highlighted beneficial effects resulting from its loss, ADCY5 was considered as promising drug target to treat diabetes. In summary, my work suggests that these positive effects are strongly dependent on the genetic background and also gender-dependent. Especially, significantly reduced voluntary exercise activity combined with readily developing DIO cast doubt on the beneficial potential of ADCY5 inhibitors.:Table of contents 1 1. Introduction 2 Obesity – a Global Pandemic 2 The Human Adipose Tissue 2 Obesity and Dysfunction of Adipose Tissue 4 Society, Environment and Genetics in the Pathogenesis of Obesity and AT Distribution 6 Rationale for Chapter 1 8 The Developmental Control Genes of the Homeobox Family 8 Aim of the Study in Chapter 1 11 Rationale for Chapter 2 11 Adenylyl Cyclases 12 How Adenylyl Cyclases Impact Diabetes 14 Aim of the Study in Chapter 2 16 The Cre-loxP System and Generation Knockout Mouse Models 17 2. Chapter 1 19 3. Chapter 2 38 4. Summary 60 5. References 65 6. Appendix 75 A. Supplementary Material - Chapter 1 75 B. Supplementary Material - Chapter 2 82 Erklärung über die eigenständige Abfassung der Arbeit 95 Curriculum Vitae 96 List of Publications and Talks 97 Danksagung 99

No description available.

O fornecimento de colostro bovino liofilizado (CBL), fonte alternativa de proteína, foi avaliado como um ingrediente inovador na nutrição de peixes. A influência desta secreção láctea foi estudada sobre o desenvolvimento dos tecidos entérico, hepático e muscular de pacu (Piaractus mesopotamicus) e dourado (Salminus brasiliensis) juvenis, utilizando-se análises da concentração sérica de IGF-I, o estudo da estrutura morfológica e atividade enzimática no intestino e, os indicadores de atividade celular nos tecidos entérico, hepático e muscular. Os pacus (8,5 ± 0,7g; 7,7 ± 0,3cm) e dourados (13,3 ± 0,9g; 10,8 ± 0,3cm), foram distribuídos num delineamento experimental inteiramente casualizado em esquema fatorial 3x2, constituindo-se de três dietas com inclusão de CBL (0%, 10% e 20%) e dois períodos experimentais (30 e 60 dias). Para os indicadores de desempenho no pacu, houve interação para ganho de peso (GP) e conversão alimentar aparente (CAA) (P<0,05). Os valores de GP, para 10 e 20% de CBL, não diferiram do 0% de CBL, indicando que as dietas foram adequadas e atenderam as necessidades nutricionais dos juvenis. Maior índice de conversão alimentar foi encontrado com 10% de CBL, aos 60 dias. A concentração de IGF-I não diferiu entre as dietas nas duas espécies, contudo, foi maior no dourado aos 60 dias (P<0,05). A morfologia do epitélio intestinal de pacu e dourado juvenis não foi alterada pelo fornecimento de CBL, entretanto, observaram-se diferenças entre os segmentos intestinais. A atividade da enzima aminopeptidase N foi maior nos pacus alimentados com 10% e 20% de CBL (P<0,05); a atividade das peptidases e dissacaridases foi menor aos 60 dias; exceto para aminopeptidase A, que apresentou elevada atividade neste mesmo período. No dourado, apenas houve diferença para aminopeptidase A, que foi menor aos 60 dias (P<0,05). Com relação aos indicadores de atividade celular, no intestino de pacu, a relação proteína total (PT)/RNA foi menor aos 30 dias. No fígado de dourado houve interação entre dieta e período para DNA, sendo maior nos peixes alimentados com 20% de CBL, aos 60 dias. No músculo de pacu PT/RNA foi maior com 10% de CBL; RNA, PT/DNA e RNA/DNA menor aos 60 dias, enquanto DNA e PT/RNA, maior neste mesmo período. No músculo do dourado, RNA e RNA/DNA, foram menores aos 60 dias e, PT/RNA, maior neste mesmo período (P<0,05). Considerando os aspectos estudados para avaliar as consequências do fornecimento de colostro bovino para pacu e dourado juvenis, observou-se que foram mantidas inalteradas a plasticidade e atividade das enzimas no epitélio intestinal e a atividade celular nos tecidos entérico, hepático e muscular. Esta condição sugere a possibilidade de uso desta secreção láctea na nutrição dos peixes estudados. / The supply of lyophilized bovine colostrum (LBC), alternative protein source, has been evaluated as an innovative ingredient in fish nutrition. The milk secretion influence was studied on enteric, liver and muscle tissues development of pacu (Piaractus mesopotamicus) and dourado (Salminus brasiliensis), using analysis of serum IGF-I concentration, morphological structure study and enzyme activity in intestine, as well as the responses of cellular indicators in enteric, liver and muscle tissues. Juveniles of pacu (8.5 ± 0.7g; 7.7 ± 0.3cm) and dourado (13.3 ± 0.9g; 10.8 ± 0.3cm) were distributed in a completely randomized design in a factorial scheme 3x2, constituting of three diets with LBC inclusion (0, 10 or 20%) and two experimental periods (30 or 60 days). The performance indicators in pacu, interaction between diet and period was observed to weight gain (WG) and feed conversion rate (FCR) (P<0.05). GP values in 10 and 20% LBC did not differ from the values of 0% LBC, indicating that the diets were adequate and met the nutritional needs of the juveniles. Higher FCR was found with 10% LBC at 60 days. IGF-I concentration did not differ between diets in both species, but was higher in dourado at 60 days (P<0.05). The pacu and dourado intestinal epithelium histomorphometry, was not altered by the LBC supply, however, there were differences between intestinal segments. The enzyme activity of aminopeptidase N was higher in pacu fed 10% and 20% of LBC (P<0.05); the activity of peptidases and disaccharidases was lower at 60 days; except for aminopeptidase A which showed high activity in this period. In the dourado, was difference only to aminopeptidase A, which was lower at 60 days (P<0.05). Regarding the indicators of cellular activity, in intestine of pacu, total protein (TP)/RNA ratio was lower at 30 days. In liver of dourado, there was interaction between diet and period for DNA, being higher in fish fed 20% LBC, at 60 days. In muscle of pacu, TP/RNA was higher with 10% LBC; RNA, TP/DNA and RNA/DNA ratio lower at 60 d, while TP and DNA/RNA ratio increased during the same period. In muscle of dourado, RNA and RNA/DNA were lower at 60 days and, TP/RNA higher in the same period (P<0.05). Considering the aspects studied to evaluate the effects of bovine colostrum for juvenile pacu and dourado, it was observed that were kept unchanged the plasticity and enzymes activity in intestinal epithelium and cellular activity in enteric, liver and muscle tissues. This condition suggests the possibility of using this milk secretion in nutrition of fish studied.

O fornecimento de colostro bovino liofilizado (CBL), fonte alternativa de proteína, foi avaliado como um ingrediente inovador na nutrição de peixes. A influência desta secreção láctea foi estudada sobre o desenvolvimento dos tecidos entérico, hepático e muscular de pacu (Piaractus mesopotamicus) e dourado (Salminus brasiliensis) juvenis, utilizando-se análises da concentração sérica de IGF-I, o estudo da estrutura morfológica e atividade enzimática no intestino e, os indicadores de atividade celular nos tecidos entérico, hepático e muscular. Os pacus (8,5 ± 0,7g; 7,7 ± 0,3cm) e dourados (13,3 ± 0,9g; 10,8 ± 0,3cm), foram distribuídos num delineamento experimental inteiramente casualizado em esquema fatorial 3x2, constituindo-se de três dietas com inclusão de CBL (0%, 10% e 20%) e dois períodos experimentais (30 e 60 dias). Para os indicadores de desempenho no pacu, houve interação para ganho de peso (GP) e conversão alimentar aparente (CAA) (P<0,05). Os valores de GP, para 10 e 20% de CBL, não diferiram do 0% de CBL, indicando que as dietas foram adequadas e atenderam as necessidades nutricionais dos juvenis. Maior índice de conversão alimentar foi encontrado com 10% de CBL, aos 60 dias. A concentração de IGF-I não diferiu entre as dietas nas duas espécies, contudo, foi maior no dourado aos 60 dias (P<0,05). A morfologia do epitélio intestinal de pacu e dourado juvenis não foi alterada pelo fornecimento de CBL, entretanto, observaram-se diferenças entre os segmentos intestinais. A atividade da enzima aminopeptidase N foi maior nos pacus alimentados com 10% e 20% de CBL (P<0,05); a atividade das peptidases e dissacaridases foi menor aos 60 dias; exceto para aminopeptidase A, que apresentou elevada atividade neste mesmo período. No dourado, apenas houve diferença para aminopeptidase A, que foi menor aos 60 dias (P<0,05). Com relação aos indicadores de atividade celular, no intestino de pacu, a relação proteína total (PT)/RNA foi menor aos 30 dias. No fígado de dourado houve interação entre dieta e período para DNA, sendo maior nos peixes alimentados com 20% de CBL, aos 60 dias. No músculo de pacu PT/RNA foi maior com 10% de CBL; RNA, PT/DNA e RNA/DNA menor aos 60 dias, enquanto DNA e PT/RNA, maior neste mesmo período. No músculo do dourado, RNA e RNA/DNA, foram menores aos 60 dias e, PT/RNA, maior neste mesmo período (P<0,05). Considerando os aspectos estudados para avaliar as consequências do fornecimento de colostro bovino para pacu e dourado juvenis, observou-se que foram mantidas inalteradas a plasticidade e atividade das enzimas no epitélio intestinal e a atividade celular nos tecidos entérico, hepático e muscular. Esta condição sugere a possibilidade de uso desta secreção láctea na nutrição dos peixes estudados. / The supply of lyophilized bovine colostrum (LBC), alternative protein source, has been evaluated as an innovative ingredient in fish nutrition. The milk secretion influence was studied on enteric, liver and muscle tissues development of pacu (Piaractus mesopotamicus) and dourado (Salminus brasiliensis), using analysis of serum IGF-I concentration, morphological structure study and enzyme activity in intestine, as well as the responses of cellular indicators in enteric, liver and muscle tissues. Juveniles of pacu (8.5 ± 0.7g; 7.7 ± 0.3cm) and dourado (13.3 ± 0.9g; 10.8 ± 0.3cm) were distributed in a completely randomized design in a factorial scheme 3x2, constituting of three diets with LBC inclusion (0, 10 or 20%) and two experimental periods (30 or 60 days). The performance indicators in pacu, interaction between diet and period was observed to weight gain (WG) and feed conversion rate (FCR) (P<0.05). GP values in 10 and 20% LBC did not differ from the values of 0% LBC, indicating that the diets were adequate and met the nutritional needs of the juveniles. Higher FCR was found with 10% LBC at 60 days. IGF-I concentration did not differ between diets in both species, but was higher in dourado at 60 days (P<0.05). The pacu and dourado intestinal epithelium histomorphometry, was not altered by the LBC supply, however, there were differences between intestinal segments. The enzyme activity of aminopeptidase N was higher in pacu fed 10% and 20% of LBC (P<0.05); the activity of peptidases and disaccharidases was lower at 60 days; except for aminopeptidase A which showed high activity in this period. In the dourado, was difference only to aminopeptidase A, which was lower at 60 days (P<0.05). Regarding the indicators of cellular activity, in intestine of pacu, total protein (TP)/RNA ratio was lower at 30 days. In liver of dourado, there was interaction between diet and period for DNA, being higher in fish fed 20% LBC, at 60 days. In muscle of pacu, TP/RNA was higher with 10% LBC; RNA, TP/DNA and RNA/DNA ratio lower at 60 d, while TP and DNA/RNA ratio increased during the same period. In muscle of dourado, RNA and RNA/DNA were lower at 60 days and, TP/RNA higher in the same period (P<0.05). Considering the aspects studied to evaluate the effects of bovine colostrum for juvenile pacu and dourado, it was observed that were kept unchanged the plasticity and enzymes activity in intestinal epithelium and cellular activity in enteric, liver and muscle tissues. This condition suggests the possibility of using this milk secretion in nutrition of fish studied.

During development of tissues, cells collectively organize to form complex patterns and morphologies. A general feature of many developing epithelia is their distinct organization into cellular compartments of different cell lineages. The interfaces between these compartments, called compartment boundaries, maintain straight and sharp morphologies. The interfaces play key roles in tissue development and pattern formation. An important model system to study the morphology of compartment boundaries during development is the wing disc of the fruit fly. Two compartment boundaries exist in the fly wing disc, the anteroposterior (AP) boundary and the dorsoventral (DV) boundary. A crucial question is how compartment boundaries are shaped and remain stable during growth. In this work, we discuss the dynamics and mechanisms of compartment boundaries in developing epithelia. We analyze the general features of interfacial phenomena in coarse- grained models of passive and active fluids. We introduce a continuum description of tissues with two cell types. This model allows us to study the propagation of interfaces due to the interplay of cell dynamics and tissue mechanics. We also use a vertex model to describe cellular compartments in growing epithelia. The vertex model accounts for cell mechanics and describes a 2D picture of tissues where the network of adherens junctions characterizes cell shapes. We use this model to study the general physical mechanisms by which compartment boundaries are shaped. We quantify the stresses in the cellular network and discuss how cell mechanics and growth influence the stress profile. With the help of the anisotropic stress profile near the interfaces we calculate the interfacial tension. We show that cell area pressure, cell proliferation rate, orientation of cell division, cell elongation created by external stress, and cell bond tension all have distinct effects on the morphology of interfaces during tissue growth. Furthermore, we investigate how much different mechanisms contribute to the effective interfacial tension. We study the mechanisms shaping the DV boundary in wing imaginal disc at different stages during the development. We analyze the images of wing discs to quantify the roughness of the DV boundary and average cell elongation in its vicinity. We quantify increased cell bond tension along the boundary and analyze the role of localized reduction in cell proliferation on the morphology of the DV boundary. We use experimentally determined values for cell bond tension, cell elongation and bias in orientation of cell division in simulations of tissue growth in order to reproduce the main features of the time-evolution of the DV boundary shape.

During development of tissues, cells collectively organize to form complex patterns and morphologies. A general feature of many developing epithelia is their distinct organization into cellular compartments of different cell lineages. The interfaces between these compartments, called compartment boundaries, maintain straight and sharp morphologies. The interfaces play key roles in tissue development and pattern formation. An important model system to study the morphology of compartment boundaries during development is the wing disc of the fruit fly. Two compartment boundaries exist in the fly wing disc, the anteroposterior (AP) boundary and the dorsoventral (DV) boundary. A crucial question is how compartment boundaries are shaped and remain stable during growth. In this work, we discuss the dynamics and mechanisms of compartment boundaries in developing epithelia. We analyze the general features of interfacial phenomena in coarse- grained models of passive and active fluids. We introduce a continuum description of tissues with two cell types. This model allows us to study the propagation of interfaces due to the interplay of cell dynamics and tissue mechanics. We also use a vertex model to describe cellular compartments in growing epithelia. The vertex model accounts for cell mechanics and describes a 2D picture of tissues where the network of adherens junctions characterizes cell shapes. We use this model to study the general physical mechanisms by which compartment boundaries are shaped. We quantify the stresses in the cellular network and discuss how cell mechanics and growth influence the stress profile. With the help of the anisotropic stress profile near the interfaces we calculate the interfacial tension. We show that cell area pressure, cell proliferation rate, orientation of cell division, cell elongation created by external stress, and cell bond tension all have distinct effects on the morphology of interfaces during tissue growth. Furthermore, we investigate how much different mechanisms contribute to the effective interfacial tension. We study the mechanisms shaping the DV boundary in wing imaginal disc at different stages during the development. We analyze the images of wing discs to quantify the roughness of the DV boundary and average cell elongation in its vicinity. We quantify increased cell bond tension along the boundary and analyze the role of localized reduction in cell proliferation on the morphology of the DV boundary. We use experimentally determined values for cell bond tension, cell elongation and bias in orientation of cell division in simulations of tissue growth in order to reproduce the main features of the time-evolution of the DV boundary shape.