Epithelio-mesenchymal interactions in the developing mouse pancreas: Morphogenesis of the adult architecture

Rose, Michael I.; Crisera, Christopher A.; Colen, Kari L.; Connelly, Patrick R.; Longaker, Michael T.; Gittes, George K.

doi:10.1016/s0022-3468(99)90372-x

Cited by 23 publications

(13 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This difference in terms of development could be due to the age of the tissues used in each study. It is now established that the in vitro developmental potential of pancreata depends of the stage at which the pancreas is harvested, the age of the mesenchyme determining the differentiation state of the final explant (35). Thus, the difference in terms of repression mediated by soluble factors between the results from Li et al (26) and the ones from the present study could be due to differences in the age of the mesenchyme.…”

Section: Discussionmentioning

confidence: 45%

The Mesenchyme Controls the Timing of Pancreatic β-Cell Differentiation

et al. 2006

View full text Add to dashboard Cite

The importance of mesenchymal-epithelial interactions in the proliferation of pancreatic progenitor cells is well established. Here, we provide evidence that the mesenchyme also controls the timing of ␤-cell differentiation. When rat embryonic pancreatic epithelium was cultured without mesenchyme, we found first rapid induction in epithelial progenitor cells of the transcription factor neurogenin3 (Ngn3), a master gene controlling endocrine cell-fate decisions in progenitor cells; then ␤-cell differentiation occurred. In the presence of mesenchyme, Ngn3 induction was delayed, and few ␤-cells developed. This effect of the mesenchyme on Ngn3 induction was mediated by cell-cell contacts and required a functional Notch pathway. We then showed that associating Ngn3-expressing epithelial cells with mesenchyme resulted in poor ␤-cell development via a mechanism mediated by soluble factors. Thus, in addition to its effect upstream of Ngn3, the mesenchyme regulated ␤-cell differentiation downstream of Ngn3. In conclusion, these data indicate that the mesenchyme controls the timing of ␤-cell differentiation both upstream and downstream of Ngn3. Diabetes 55:582-589, 2006

show abstract

Section: Discussionmentioning

confidence: 45%

The Mesenchyme Controls the Timing of Pancreatic β-Cell Differentiation

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The presence of PDX-1-positive lumenal epithelium, hormone-positive cell clusters and pancreatic acini in ES cell tumours indicates that the insulin-positive cells most likely arose from pancreas morphogenesis and not merely by cytodifferentiation. Additional support for this conclusion comes from both tissue reconstitution and genetic experiments [21][22][23] that have definitively demonstrated that pancreatic mesenchyme is required for exocrine, but not endocrine, differentiation. Subcutaneous ES cell tumours that formed at the ES cell injection site in both STZ-treated and non-treated mice revealed no evidence of pancreatic differentiation (data not shown), indicating that factors produced by the regenerating pancreas were required for the ES cell differentiation and suggesting that these factors may be more effective at close range.…”

Section: Discussionmentioning

confidence: 99%

Streptozotocin-induced partial beta cell depletion in nude mice without hyperglycaemia induces pancreatic morphogenesis in transplanted embryonic stem cells

Takeshita¹,

Kodama²,

Yamamoto³

et al. 2006

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis It appears that the adult pancreas has limited regenerative ability following beta cell destruction by streptozotocin (STZ). However, it is not clear if this limitation is due to an inability to respond to, rather than an absence of, regenerative stimuli. In this study we aimed to uncouple the regenerative signal from the regenerative response by using an exogenous stem cell source to detect regenerative stimuli produced by the STZ-injured pancreas at physiological blood glucose levels. Method Adult nude mice received 150 mg/kg STZ and 1Â10 6 J1 mouse embryonic stem (ES) cells by i.p. injection. Permanent beta cell depletion of 50% was estimated from the ratio of beta:alpha cells in pancreata from STZ-treated mice compared with control animals after 24 days. Results Transplanted ES cells homed to the STZ-injured pancreas and formed tumours. Immunocytochemical analysis of pancreas-associated ES tumours revealed foci containing insulin/PDX-1 double-positive and glucagonpositive/PDX-1-negative cell clusters associated with PDX-1-positive columnar lumenal epithelium and extensive α-amylase-positive pancreatic acini comprising approximately 0.1% of ES tumour volume. Conclusions/interpretation These data indicate that (1) the adult pancreas produces a milieu of regenerative stimuli following beta cell destruction, and (2) this is not dependent on hyperglycaemic conditions; (3) these regenerative stimuli appear to recapitulate the signalling pathways of embryonic development, since both exocrine and endocrine lineages are produced from PDX-1-positive precursor epithelium. This model will be useful for characterising the regenerative mechanisms in the adult pancreas.

show abstract

“…Embryonic pancreatogenesis is complex, requiring signaling from non-endodermal (Kim et al 1997) sources and mesenchymal stimulation (Rose et al 1999), and it is exceedingly difficult to produce insulin 1 cells through spontaneous differentiation (Kahan et al 2003;Micallef et al 2005). ES were reported to be able to produce insulin-expressing cells only when combined with rudiments of embryonic pancreas (but not liver or telencephalon) under the renal capsule in vivo, and this morphogenesis did not apparently occur in ES when transplanted alone (Brolen et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Pancreatic Endocrine and Exocrine Cell Ontogeny From Renal Capsule–transplanted Embryonic Stem Cells in Streptozocin-injured Mice

Kodama¹,

Takeshita

Kanegasaki³

et al. 2007

J Histochem Cytochem.

View full text Add to dashboard Cite

S U M M A R Y In this study, we describe pancreatic cell ontogeny in renal capsule-transplanted embryonic stem cells (ES) after injury by streptozocin (STZ), showing pancreatogenesis in situ. Seven-week-old female BALB/c nude mice were treated with either a single 175-or 200-mg/ kg STZ dose, a regimen that induces substantial b-cell damage without overt hyperglycemia, and transplanted 24 hr later with 1 3 10 5 ES. Immunohistochemistry was performed on ES tissue at 15, 21, and 28 days after transplantation using antibodies against stage-and lineagespecific pancreatic markers. After 21 days, PDX-11 pancreatic foci first appeared in the renal capsule and expressed both amylase and endocrine hormones (insulin, glucagon, and somatostatin). These foci increased in size by day 28 because of acinar and duct cell proliferation, whereas endocrine cells remained non-dividing, and made up 2-4% of ES tumor volume. PDX-1, Nkx6.1, Ngn3, and ISL-1 protein localization patterns in pancreatic foci were comparable with embryonic pancreatogenesis. A prevalence of multihormonal endocrine cells, a characteristic of adult b-cell regeneration, indicated a possible divergence from embryonic islet cell development. The results indicate that b-cell damage, without overt hyperglycemia, induces a process of fetal-like pancreatogenesis in renal capsule-transplanted ES, leading to b-cell neogenesis. (J Histochem Cytochem 56:33-44, 2008)

show abstract

Epithelio-mesenchymal interactions in the developing mouse pancreas: Morphogenesis of the adult architecture

Cited by 23 publications

References 19 publications

The Mesenchyme Controls the Timing of Pancreatic β-Cell Differentiation

The Mesenchyme Controls the Timing of Pancreatic β-Cell Differentiation

Streptozotocin-induced partial beta cell depletion in nude mice without hyperglycaemia induces pancreatic morphogenesis in transplanted embryonic stem cells

Pancreatic Endocrine and Exocrine Cell Ontogeny From Renal Capsule–transplanted Embryonic Stem Cells in Streptozocin-injured Mice

Contact Info

Product

Resources

About