No. 1: Migration and Development in Africa: An Overview

Migration is clearly a major issue across Africa. Indeed, migration – both within countries and across borders – can be seen as an integral part of labour markets and livelihoods across much of the continent for at least the last century. Over time, and in different places, migration has taken a number of different forms. It has cut across class and skill boundaries, and exists in widely different geographical and demographic contexts. Migration represents an important livelihood strategy for poor households seeking to diversify their sources of income, but is also characteristic of the better off, and indeed of many African elites. In practice, however, the link between migration and poverty is often viewed more negatively. It is assumed across much of the continent that it is poverty that forces poor people to migrate, rather than migration being a potential route out of poverty. The poor are also generally seen as those worst affected by conflict-induced migration, itself a prominent feature in Africa. The movement of skilled and/or wealthy Africans is also generally viewed negatively (e.g. there is long-standing concern on the African continent with the impact of the ‘brain drain’ of African professionals). Only slowly, and in relatively few quarters, is understanding emerging of the potentially positive role that migration itself can play in reducing poverty, or of the possibilities for ‘mobilisation’ of the African diaspora in the fight against poverty. Meanwhile, public policy remains a long way from building effectively on such understanding. The aim of this study is to synthesise existing research on migration in Africa, and its relationship to development policy. The report focuses on the relationship between migration, poverty and pro-poor development policy. Pro-poor policy is taken here to mean policies that are context-specific, listen and react to poor people’s voices, and/or seek to assist poor people to become less vulnerable and build up their income and assets. Government health and education policies might not be considered intrinsically pro-poor, but become so where they are targeted at widening access to health and education services, and especially basic health and education services (e.g. primary care, vaccination campaigns, primary schooling), or at responding to the specific needs of the poor. Pro-poor policies might also seek to identify and support poor people’s livelihoods, through the promotion of social protection mechanisms (ranging from pensions, health insurance, maternity benefit and unemployment benefits to food aid and other social assistance) or enhancement and enforcement of poor people’s rights. In turn, our focus is not only on the policies of developing country governments, but also on those of non-government and intergovernmental organisations, and of donor nations. In terms of migration, the study covers both international and internal migration. In the sections that follow, issues are dealt with first in relation to sub-Saharan Africa as a whole, and then in detail for three regions – West Africa, East Africa and Southern Africa. The sections on Africa as a whole, and on West and East Africa were completed by researchers at the Sussex Centre for Migration Research at the University of Sussex, whilst the section on Southern Africa was written by researchers at the Southern African Migration Project

Developmental SMAD6 loss leads to blood vessel hemorrhage and disrupted endothelial cell junctions

The BMP pathway regulates developmental processes including angiogenesis, yet its signaling outputs are complex and context-dependent. Recently, we showed that SMAD6, an intracellular BMP inhibitor expressed in endothelial cells, decreases vessel sprouting and branching both in vitro and in zebrafish. Genetic deletion of SMAD6 in mice results in poorly characterized cardiovascular defects and lethality. Here, we analyzed the effects of SMAD6 loss on vascular function during murine development. SMAD6 was expressed in a subset of blood vessels throughout development, primarily in arteries, while expression outside of the vasculature was largely confined to developing cardiac valves with no obvious embryonic phenotype. Mice deficient in SMAD6 died during late gestation and early stages of postnatal development, and this lethality was associated with vessel hemorrhage. Mice that survived past birth had increased branching and sprouting of developing postnatal retinal vessels and disorganized tight and adherens junctions. In vitro, knockdown of SMAD6 led to abnormal endothelial cell adherens junctions and increased VE-cadherin endocytosis, indicative of activated endothelium. Thus, SMAD6 is essential for proper blood vessel function during murine development, where it appears to stabilize endothelial junctions to prevent hemorrhage and aberrant angiogenesis

Flt-1 (Vascular Endothelial Growth Factor Receptor-1) Is Essential for the Vascular Endothelial Growth Factor-Notch Feedback Loop During Angiogenesis

OBJECTIVE: Vascular endothelial growth factor (VEGF) signaling induces Notch signaling during angiogenesis. Flt-1/VEGF receptor-1 negatively modulates VEGF signaling. Therefore, we tested the hypothesis that disrupted Flt-1 regulation of VEGF signaling causes Notch pathway defects that contribute to dysmorphogenesis of Flt-1 mutant vessels. APPROACH AND RESULTS: Wild-type and flt-1(-/-) mouse embryonic stem cell-derived vessels were exposed to pharmacological and protein-based Notch inhibitors with and without added VEGF. Vessel morphology, endothelial cell proliferation, and Notch target gene expression levels were assessed. Similar pathway manipulations were performed in developing vessels of zebrafish embryos. Notch inhibition reduced flt-1(-/-) embryonic stem cell-derived vessel branching dysmorphogenesis and endothelial hyperproliferation, and rescue of flt-1(-/-) vessels was accompanied by a reduction in elevated Notch targets. Surprisingly, wild-type vessel morphogenesis and proliferation were unaffected by Notch suppression, Notch targets in wild-type endothelium were unchanged, and Notch suppression perturbed zebrafish intersegmental vessels but not caudal vein plexuses. In contrast, exogenous VEGF caused wild-type embryonic stem cell-derived vessel and zebrafish intersegmental vessel dysmorphogenesis that was rescued by Notch blockade. CONCLUSIONS: Elevated Notch signaling downstream of perturbed VEGF signaling contributes to aberrant flt-1(-/-) blood vessel formation. Notch signaling may be dispensable for blood vessel formation when VEGF signaling is below a critical threshold

Flt-1 (VEGFR-1) coordinates discrete stages of blood vessel formation

In developing blood vessel networks, the overall level of vessel branching often correlates with angiogenic sprout initiations, but in some pathological situations, increased sprout initiations paradoxically lead to reduced vessel branching and impaired vascular function. We examine the hypothesis that defects in the discrete stages of angiogenesis can uniquely contribute to vessel branching outcomes

Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6

Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFβ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD transcription factors (R-SMAD1/5/8) and regulate vessel growth. However, SMAD1/5/8 signalling results in both pro- and anti-angiogenic outputs, highlighting a poor understanding of the complexities of BMP signalling in the vasculature. Here we show that BMP6 and BMP2 ligands are pro-angiogenic in vitro and in vivo, and that lateral vessel branching requires threshold levels of R-SMAD phosphorylation. Endothelial cell responsiveness to these pro-angiogenic BMP ligands is regulated by Notch status and Notch sets responsiveness by regulating a cell-intrinsic BMP inhibitor, SMAD6, which affects BMP responses upstream of target gene expression. Thus, we reveal a paradigm for Notch-dependent regulation of angiogenesis: Notch regulates SMAD6 expression to affect BMP responsiveness of endothelial cells and new vessel branch formation

Automatic identification of species-specific repetitive DNA sequences and their utilization for detecting microbial organisms

Motivation: The concentration of pathogen DNA in biological samples is often very low. Therefore, the sensitivity of diagnostic tests is always a critical factor

Mutation in utp15 Disrupts Vascular Patterning in a p53-Dependent Manner in Zebrafish Embryos

Angiogenesis is the process by which the highly branched and functional vasculature arises from the major vessels, providing developing tissues with nutrients, oxygen, and removing metabolic waste. During embryogenesis, vascular patterning is dependent on a tightly regulated balance between pro- and anti-angiogenic signals, and failure of angiogenesis leads to embryonic lethality. Using the zebrafish as a model organism, we sought to identify genes that influence normal vascular patterning.In a forward genetic screen, we identified mutant LA1908, which manifests massive apoptosis during early embryogenesis, abnormal expression of several markers of arterial-venous specification, delayed angiogenic sprouting of the intersegmental vessels (ISV), and malformation of the caudal vein plexus (CVP), indicating a critical role for LA1908 in cell survival and angiogenesis. Genetic mapping and sequencing identified a G to A transition in the splice site preceding exon 11 of utp15 in LA1908 mutant embryos. Overexpression of wild type utp15 mRNA suppresses all observed mutant phenotypes, demonstrating a causative relationship between utp15 and LA1908. Furthermore, we found that injecting morpholino oligonucleotides inhibiting p53 translation prevents cell death and rescues the vascular abnormalities, indicating that p53 is downstream of Utp15 deficiency in mediating the LA1908 phenotypes.Taken together, our data demonstrate an early embryonic effect of Utp15 deficiency on cell survival and the normal patterning of the vasculature and highlight an anti-angiogenic role of p53 in developing embryos

Venous identity requires BMP signalling through ALK3

Venous endothelial cells are molecularly and functionally distinct from their arterial counterparts. Although veins are often considered the default endothelial state, genetic manipulations can modulate both acquisition and loss of venous fate, suggesting that venous identity is the result of active transcriptional regulation. However, little is known about this process. Here we show that BMP signalling controls venous identity via the ALK3/BMPR1A receptor and SMAD1/SMAD5. Perturbations to TGF-β and BMP signalling in mice and zebrafish result in aberrant vein formation and loss of expression of the venous-specific gene Ephb4, with no effect on arterial identity. Analysis of a venous endothelium-specific enhancer for Ephb4 shows enriched binding of SMAD1/5 and a requirement for SMAD binding motifs. Further, our results demonstrate that BMP/SMAD-mediated Ephb4 expression requires the venous-enriched BMP type I receptor ALK3/BMPR1A. Together, our analysis demonstrates a requirement for BMP signalling in the establishment of Ephb4 expression and the venous vasculature

Exploring Regional Food Systems: A North Country Example

CaRDI Research & Policy Brief Issue 2

CaRDI’s Support for Community Economic Development

CaRDI Research & Policy Brief Issue 3