The Effect of Retinoic Acid on the Proportion of Insulin Cells in the Developing Chick Pancreas

Penny, Clem; Kramer, Beverley

doi:10.1290/1071-2690(2000)036<0014:teorao>2.0.co;2

Cited by 13 publications

(8 citation statements)

References 42 publications

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“…Several factors have been shown to promote b-cell differentiation and insulin production including activin A (a member of the TGF-b superfamily; Penny and Kramer, 2002), nicotinamide (Mngomezulu and Kramer, 2000) and RA (Penny and Kramer, 2000). Initially, we wanted to determine if any of these factors could affect exocrine or endocrine (specifically b cell) differentiation in our culture system.…”

Section: Development Of Pancreatic Buds In Vitromentioning

confidence: 99%

“…This is partly related to the use of different species (e.g., mouse, rat, chick, and Xenopus) as well as differences in model systems (e.g., culture in collagen or Matrigel) and the use of varying concentrations of 9-cis RA or atRA (1 nM-5 mM). For example, addition of atRA was reported to increase the proportion of insulin cells in Xenopus and chick, but not in mouse (Penny and Kramer, 2000;Kadison et al, 2001;Kramer and Penny, 2003;Chen et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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All-trans retinoic acid suppresses exocrine differentiation and branching morphogenesis in the embryonic pancreas

Shen¹,

Marguerie²,

Chien³

et al. 2007

Differentiation

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Recent evidence has shown that retinoic acid (RA) signalling is required for early pancreatic development in zebrafish and frog but its role in later development in mammals is less clear cut. In the present study, we determined the effects of RA on the differentiation of the mouse embryonic pancreas. Addition of all-trans retinoic acid (atRA) to embryonic pancreatic cultures induced a number of changes. Branching morphogenesis and exocrine differentiation were suppressed and there was premature formation of endocrine cell clusters (although the total area of b cells was not different in control and atRA-treated buds). We investigated the mechanism of these changes and found that the premature formation of b cells was associated with the early expression of high-level Pdx1 in the endocrine cell clusters. In contrast, the suppressive effect of RA on exocrine differentiation may be due to a combination of two mechanisms (i) up-regulation of the extracellular matrix component laminin and (ii) enhancement of apoptosis. We also demonstrate that addition of fibroblast growth factor (FGF)-10 is able to partially prevent apoptosis and rescue exocrine differentiation and branching morphogenesis in atRA-treated cultures but not in mice lacking the FGF receptor 2-IIIb, suggesting the effects of FGF-10 are mediated through this receptor.

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Section: Development Of Pancreatic Buds In Vitromentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

All-trans retinoic acid suppresses exocrine differentiation and branching morphogenesis in the embryonic pancreas

Shen¹,

Marguerie²,

Chien³

et al. 2007

Differentiation

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“…A critical regulator of pancreatic endoderm specification and commitment to the endocrine lineage is retinoic acid (RA) signalling. RA signalling has been extensively examined for its effects on pancreas specification in chick [24], frog [25], fish [26][27][28] and mouse [29][30][31], and demonstrated to be an important early specifying agent in these contexts. In studies designed to eliminate endogenous RA production during embryonic foregut endoderm differentiation, the enzyme responsible for foregut RA synthesis (RALDH2) was knocked out.…”

Section: The Third Step Pancreatic Epithelium and Endocrine Precursorsmentioning

confidence: 99%

Production of β‐cells from human embryonic stem cells

Baetge¹

2008

Diabetes Obesity Metabolism

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The making of functional pancreatic islets in renewable numbers has been a goal of stem cell biologists since early 2000. Since that time, many studies have reported successful creation of glucose-responsive pancreatic b-cells. Not until the more recent systematic application of developmental principles to stem cell biology systems were breakthroughs achieved on directed specification of the required early developmental intermediates. The most important first step is the formation of the definitive endoderm (DE) lineage which is compulsory for production of the epithelium of the pancreas and the other important endoderm-derived organs such as the liver, intestine and lung. The formation of DE from embryonic stem cells made possible additional experimentation aimed at directing the endoderm to further specified foregut and pancreatic endoderm lineages. With these discoveries came the first production of immature pancreatic endocrine cells. Most recently, the production in vivo of glucose-responsive insulin-producing cells with the capacity to correct Steptozotocin-induced hyperglycaemia in mice has been achieved. The work leading up to this achievement, in relation to the other principle human stem cell studies conducted in this area, will be briefly described. The necessary steps and ideal characteristics of embryonic stem cell-based differentiation to pancreatic b-cells capable of glucose stimulated insulin secretion will be underscored.

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“…In the following studies in which the endodermal component of embryonic chick dorsal pancreatic buds were cultured on Matrigel, with different nutrients, vitamins or hormones added to the serumfree medium, an increase in the proportion of insulin cells occurred. For example, this occurred with raised essential amino acids and, in particular, raised glucose (Rawdon & Andrew 1997), tri-iodothyronine with increased glucose and essential amino acids (Rawdon & Andrew 1998) and with retinoic acid (Penny & Kramer 2000). An increase in the proportion of insulin cells was also achieved with explants grown on Matrigel with reduced growth factors and with insulin-like growth factor I added to the serum-free medium (Rawdon & Andrew 1998).…”

Section: Introductionmentioning

confidence: 99%

Beneficial effect of nicotinamide on the proportion of insulin cells in developing chick pancreas

Mngomezulu

Kramer

2000

Dev Growth Differ

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Previous studies have suggested that nicotinamide increases the number of insulin cells both in vivo and in vitro. However, the question remains as to whether there is in fact an increase and whether this increase is caused by the proliferation of progenitor cells, or by replication of existing insulin cells. In order to investigate this, the endodermal component of dorsal pancreatic buds of 5-day-old chick embryos was cultured on Matrigel in a serum-free medium (Ham's F12-ITS) to which nicotinamide, at a concentration of 5 and 10 mM, respectively, was added. Control explants were cultured in Ham's F12-ITS medium without nicotinamide. After 7 days in culture the buds were incubated with bromodeoxyuridine (BrdU) and then processed for immunocytochemistry. Localization of insulin, BrdU and glucagon was carried out on adjacent serial sections. The proportion of insulin cells was 6.76, 11.32 and 16.86% in control, 5 and 10 mM nicotinamide-treated explants, respectively. Hence adding nicotinamide to the culture medium induced a 1.7- and 2.5-fold increase in the proportion of insulin cells when compared to the controls. These proportions were significantly different from that of control explants (P < 0.05). However, a very small number of insulin cells were found to be proliferating, suggesting that the increase in the proportion of insulin cells had resulted from stimulation of progenitor cells and not proliferation of existing insulin cells.

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The Effect of Retinoic Acid on the Proportion of Insulin Cells in the Developing Chick Pancreas

Cited by 13 publications

References 42 publications

All-trans retinoic acid suppresses exocrine differentiation and branching morphogenesis in the embryonic pancreas

All-trans retinoic acid suppresses exocrine differentiation and branching morphogenesis in the embryonic pancreas

Production of β‐cells from human embryonic stem cells

Beneficial effect of nicotinamide on the proportion of insulin cells in developing chick pancreas

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