Browsing by Subject "Development"

Now showing 1 - 7 of 7

ATP4 and Wnt-signaling are required for ciliogenesis and left-right axis development of Xenopus
(2012) Walentek, Peter; Blum, Martin
The vertebrate body plan displays left-right (LR) asymmetries of organ placement superimposed on an overt bilaterally symmetrical organization. Symmetry is broken during embryogenesis, and asymmetric gene expression precedes asymmetric organ morphogenesis. The proton/potassium pump ATP4 was shown to play a role in LR-development of the frog Xenopus laevis as well as in other deuterostomes. Two opposing models of symmetry-breakage were proposed, the ?ion-flux? and the ?leftward flow? model. The former proposed that symmetry was broken by LR-asymmetric expression of the a-subunit of ATP4 during cleavage stages. The latter claimed a cilia-based leftward flow at the gastrocoel roof plate (GRP) to take center stage during neurulation, i.e. a day later in development. In the present thesis work, the role of ATP4a in symmetry-breakage was re-addressed and evidence for symmetrical expression and function of ATP4a was gathered. ATP4a was shown to be required for two Wnt-signaling dependent steps during the setup of cilia driven leftward flow at the GRP: (1) Wnt/b-catenin (b-cat) dependent expression of Foxj1 during gastrulation, and (2) Wnt/planar cell polarity (PCP) dependent posterior localization of motile cilia during neurulation. These data challenge the ?ion-flux? hypothesis and argue for a conserved ATP4- and cilia-dependent symmetry-breakage mechanism throughout the vertebrates. Furthermore, the function of Wnt-signaling components was analyzed in the context of GRP-formation: The receptor Frizzled 8 (Fz8) and b-cat were required for Foxj1 expression during gastrulation. Morphogenesis of the GRP, posterior polarization of motile cilia and expression of Xnr1 and Coco in somitic cells were all required for LR-development. Loss of non-canonical Xwnt11b-signaling perturbed these process, suggesting that non-canonical Wnt-signaling branches, in addition to Wnt/PCP, were relevant for LR-development. ATP4-mediated Wnt-signaling was also required for Foxj1 expression and motile cilia in other epithelia during Xenopus development, i.e. the skin, floor plate and the ependymal cell layer. In the floor plate b-cat was required for Foxj1 expression downstream of Hedgehog-signaling. In the skin mucociliary epithelium ATP4a and Wnt/b-cat were required downstream of Notch/Delta-mediated cell-type specification of multiciliated cells. This was also true for a new cell type of serotonergic cells described here, which was characterized morphologically, by analysis of gene expression and response to manipulations of Wnt- and Notch/Delta-signaling. In summary, the data presented in this thesis suggest a conserved function of ATP4a and Wnt-signaling in vertebrate symmetry-breakage and Foxj1-dependent ciliogenesis in Xenopus.
Delimitation of the organizer from the posterior notochord : descriptive and functional studies in mouse and African clawed frog
(2009) Andre, Philipp; Blum, Martin
During vertebrate development, gastrulation is probably the most important phase, as the future body plan is established. Thereby the three body axes anterior-posterior, dorsal-ventral and left-right are determined as well. A central role thereby is taken by the Spemann organizer, as this part of the embryo governs the above mentioned processes. The left-right axis is specified by an extracellular leftward fluid-flow, which results in asymmetric gene expression of the TGFβ factor Nodal. In mice the ciliated epithelium responsible for the fluid-flow as well as the organizer are denominated as ?node?. In contrast to that two distinct entities are thought to be responsible for organizer function and fluid-flow in zebrafish, Xenopus and rabbit embryos. In the present study, it could be shown that this also applies for mouse embryos. In order to prevent further confusion the ciliated epithelium responsible for the fluid-flow was denominated as posterior notochord (PNC) as it is in continuity with the notochord but located anterior to the organizer (?node?). The latter is characterized by the expression of the homeobox gene Goosecoid (Gsc). Gsc possesses, like the tissue of the organizer, the potential to induce an almost complete axis and became therefore famous as ?the organizer gene?. However upon knockout of Gsc in the mouse, surprisingly no gastrulation defects could be detected. Therefore the function of Gsc during gastrulation was investigated using a gain-of-function approach. The analysis of this, in the present and previous studies, indicated that Gsc acts as a switch between two modes of cell movement. Accordingly, Gsc promotes active cell migration and inhibits convergent extension movements. Furthermore it was investigated whether the monoamines adrenaline and serotonin have an influence on the cilia and thus on the leftward fluid-flow, as it was reported in rat and Xenopus experiments. Thereby it could be detected that the addition of adrenaline led to a reduction of the ciliary beat frequency (CBF) and therefore the fluid-flow was attenuated. In contrast to that the addition of serotonin or its antagonists resulted only in minor changes of CBF and thus had no measurable effect on the fluid-flow. The consequences of a malformed PNC were analyzed using embryos mutant for Brachyury (T). Thereby, it was shown that embryos homozygous for this mutation did not develop a functional PNC and thus lacked the fluid-flow. Furthermore a possible cause for the absence of asymmetric Nodal in these embryos was brought into context of an attenuated expression of Fgf8. This indicated that T possesses two distinct roles in left-right development. On the one hand it is necessary for the correct formation of a PNC and on the other hand it is probably needed to maintain the expression of Fgf8, which is a prerequisite for the transcription of Nodal. Finally it was investigated whether these functions were conserved from the African clawed frog Xenopus. Thereby, it could be shown, that Xbra, the homologous gene of T in Xenopus, was also necessary for the formation of the gastrocoel roof plate, the homologous structure of the PNC. Additionally it was observed that the absence of Xbra led to an attenuation of Nodal expression in the midline of Xenopus embryos. This implied that not only the function of Brachyury, but also the process of laterality determination is highly conserved between mammals and amphibians.
Go east : on the impact of the Transiberian Railway on economic development in Eastern Russia
(2019) Seiffert, Sebastian
This paper addresses the question whether or not large-scale infrastructure investments have a causal effect of local economic development. By using a novel instrumental variable approach based on historical trade and travel routes across the Russian East, I am able to identify a causal and negative effect of remoteness to the Transsiberian Railway on local economic activity as measured by nocturnal lights emission.
Illuminating the World Cup effect : night lights evidence from South Africa
(2016) Pfeifer, Gregor; Wahl, Fabian; Marczak, Martyna
This paper evaluates the economic impact of the $14 billion preparatory investments for the 2010 FIFA World Cup in South Africa. We use satellite data on night light luminosity at municipality and electoral district level as a proxy for economic development, applying synthetic control methods for estimation. For the average World Cup municipality, we find significantly positive, short-run effects before the tournament, corresponding to a reduction of unemployment by 1.3 percentage points. At the electoral district level, we reveal distinct effect heterogeneity, where especially investments in transport infrastructure are shown to have long-lasting, positive effects, particularly in more rural areas.
Non-financial hurdles for human capital accumulation : landownership in Korea under Japanese rule
(2014) Kim, Tai-Yoo; Jun, Bogang
This paper suggests that inequality in landownership is a nonfinancial hurdle for human capital accumulation. It is the first to present evidence that inequality in landownership had an adverse effect on the level of public education in the Korean colonial period. Using a fixed effects model, the present research exploits variations in inequality in land concentration across regions in Korea and accounts for the unobserved heterogeneity across these regions. The analysis establishes a highly significant adverse effect of Land inequality on education in the Korean colonial period.
Regional development perspectives in Vietnam: insights from a 2002 provincial social accounting matrix (SAM)
(2004) Heidhues, Franz; Breisinger, Clemens
Growing regional disparities in Vietnam have encouraged plans to extend the national Comprehensive Poverty Reduction and Growth Strategies (CPRGS) to the provincial level. The northern mountainous province of Son La has distinctive development perspectives. It was selected as the site of Vietnam?s planned biggest dam and hydroelectric power plant. Large-scale infrastructure investments are expected to contribute to economic growth and poverty reduction in the region. The impacts of these investments on the regional economy can be assessed with a multiplier model based on a regional social accounting matrix (SAM). In this paper, we present a 2002 SAM for Son La. To shed light on the socioeconomic situation, we review insights from this detailed database. A SAM-based multiplier model is then put forward to examine linkages within the provincial economy and to present first results of demand-side effects of infrastructure investment in the local construction sector.
Was war falsch am Merkantilismus?
(2018) Spahn, Peter
Mercantilist theories and policies in early capitalism have been criticized for confusing microeconomic and macroeconomic sources of wealth, for misunderstanding the benefits of free trade, and for overrating the role of money. This paper aims to reconstruct the rationality of mercantilism as an efficient strategy of economic development. It presents a critical assessment of David Hume’s specie flow mechanism that counts as a major rebuttal of mercantilism and collects insights of early writers into the working of a monetary economy.