Induction of Pancreatic Differentiation by Signals from Blood Vessels

Lammert, Eckhard; Cleaver, Ondine; Melton, Douglas A.

doi:10.1126/science.1064344

Cited by 981 publications

(861 citation statements)

References 19 publications

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“…We have indeed shown that taurine restored fetal islet vascularisation altered by an LP diet, as well as expression of IGF-2 and vascular endothelial growth factor [5,24]. Vascularisation and vascular endothelial growth factor are of prime importance for the differentiation of the endocrine pancreas [31], and IGFs, being mitogenic and survival factors, modulate the mass of islet cells [6,32]. Different levels of taurine during development may thus provide different populations of islet cells, resulting from an activity of this amino acid on these factors.…”

Section: Discussionmentioning

confidence: 59%

Effect of maternal low-protein diet and taurine on the vulnerability of adult Wistar rat islets to cytokines

et al. 2004

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Aims/hypothesis. A maternal low-protein diet has been shown to induce an increased susceptibility of fetal islets to cytokines, but this effect can be avoided by maternal taurine supplementation. Here, we question whether these effects persist until adulthood in the offspring, despite the animal having a normal diet after weaning. Methods. Pregnant Wistar rats received a diet of either 20% or 8% protein (control [C group] and recuperated [R group] respectively), which was or was not supplemented with taurine (control treated with taurine [CT group] and recuperated treated with taurine [RT group] respectively) during gestation and lactation. When the female offspring reached adulthood, an OGTT was performed. In a second stage, islets were isolated from these offspring, then pretreated or not with taurine, and subsequently treated with cytokines. Results. Fasting glycaemia was higher (p<0.05) and insulinaemia was lower (p<0.01) in the R group than in the C group. Taurine supplementation decreased insulinaemia in the CT group and tended to increase it in the RT group. After the OGTT, glycaemia in R animals was not different from that in the C group, despite a blunted insulin response (p<0.05) which was restored by taurine. Supplementation in C-group mothers led to a weak glucose intolerance. In vitro, more apoptotic cells were observed in R islets after cytokines treatment (p<0.01). The addition of taurine to the culture medium in the R and C groups protected the islets from the cytokines (p<0.01). Maternal taurine supplementation decreased the sensitivity of islets in the RT group (p<0.01), but increased sensitivity in the CT group (p<0.01). Conclusions/interpretation. The increased vulnerability of islets to cytokines due to a restriction of protein during fetal development was still evident when the offspring reached adulthood. The low-protein diet also induced hyperglycaemia in the presence of lower insulinaemia. Taurine supplementation protected adult islets of the R group from cytokine toxicity and restored the insulinaemia. However, unnecessary supplementation of taurine could have detrimental effects.

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Section: Discussionmentioning

confidence: 59%

Effect of maternal low-protein diet and taurine on the vulnerability of adult Wistar rat islets to cytokines

et al. 2004

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“…For example, aorta-less Xenopus embryos failed to Developmental Dynamics express pancreatic genes, and co-culture of mouse dorsal prepancreatic endoderm with dorsal aortae could induce Pdx1 and insulin expression (Lammert et al, 2001). Furthermore, it was also shown that misexpression of VEGF-A (under a Pdx1 promoter) in transgenic mice caused islet hyperplasia and ectopic insulin þ cells in the stomach.…”

Section: Dorsal Pancreas Induction: Signaling From Notochord and Vascmentioning

confidence: 99%

“…[In mouse, some report that two ventral pancreas ''buds'' are first formed, with one regressing during gut rotation (Lammert et al, 2001), in association with the process of the dorsal to ventral pancreas joining that occurs at $E12.5.] Shortly after E9.5, the buds grow out into the adjacent mesenchyme, forming essentially ''solid buds'' of stratified epithelium.…”

Section: Pancreas Budding and The Primary Transitionmentioning

confidence: 99%

Pancreas organogenesis: From bud to plexus to gland

Pan

Wright

2011

Developmental Dynamics

528

594

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Pancreas oganogenesis comprises a coordinated and highly complex interplay of signaling events and transcriptional networks that guide a step-wise process of organ development from early bud specification all the way to the final mature organ state. Extensive research on pancreas development over the last few years, largely driven by a translational potential for pancreatic diseases (diabetes, pancreatic cancer, and so on), is markedly advancing our knowledge of these processes. It is a tenable goal that we will one day have a clear, complete picture of the transcriptional and signaling codes that control the entire organogenetic process, allowing us to apply this knowledge in a therapeutic context, by generating replacement cells in vitro, or perhaps one day to the whole organ in vivo. This review summarizes findings in the past 5 years that we feel are amongst the most significant in contributing to the deeper understanding of pancreas development. Rather than try to cover all aspects comprehensively, we have chosen to highlight interesting new concepts, and to discuss provocatively some of the more controversial findings or proposals. At the end of the review, we include a perspective section on how the whole pancreas differentiation process might be able to be unwound in a regulated fashion, or redirected, and suggest linkages to the possible reprogramming of other pancreatic cell-types in vivo, and to the optimization of the forward-directed-differentiation of human embryonic stem cells (hESC), or induced pluripotential cells (iPSC), towards mature b-cells. Developmental Dynamics 240:530-565,

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“…Evidence that endothelial cells are required for stem cell function comes from studies of developing islets of Langerhans and liver. The islets of Langerhans fail to develop in frogs in which the dorsal aorta has been ablated (27). Similarly, liver fails to develop in mice in which blood vessels do not develop (28).…”

Section: Discussionmentioning

confidence: 99%

“…The failure of development of these organs in the absence of blood vessels occurs at a time before blood begins to flow, suggesting that the failure of development is not the result of a lack of blood-derived nutrients, but due to the absence of endothelial-derived signals. Signals from the blood vessels induce the ectopic development of islets of Langerhans in developing gut (27), and overgrowth of the liver (29). Additional evidence that blood vessels are important for stem cell function comes from studies of neuronal stem cells.…”

Section: Discussionmentioning

confidence: 99%