Early pancreas organogenesis: Morphogenesis, tissue interactions, and mass effects

Wessells, Norman K.; Cohen, Julia H.

doi:10.1016/0012-1606(67)90042-5

Cited by 295 publications

(146 citation statements)

References 30 publications

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“…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

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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.

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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

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“…The region of the gut epithelium fated to form the dorsal pancreatic bud is initially in direct contact with the notochord (29,30), and notochord-derived factors, such as activin-␤ and fibroblast growth factor (FGF)-2, have been implicated in the initial repression of Shh and Ihh expression in the presumptive dorsal pancreatic endoderm (31)(32)(33). In contrast, the ventral gut epithelium destined to form the ventral pancreatic bud is never contacted by the notochord, implying that the exclusion of Shh and Ihh gene expression from the ventral pancreatic epithelium is achieved by a distinct notochord-independent mechanism.…”

Section: Initiation Of the Pancreatic Programmentioning

confidence: 99%

Developmental biology of the pancreas.

2001

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All pancreatic cell types (endocrine, exocrine, and ductal) are derived from the same endodermal dorsal and ventral anlage, which grow together to form the definitive pancreas. Golosow and Grobstein were pioneers in the field of pancreatic developmental research, as were Wessells and Cohen, who already in the 1960s performed classic embryological experiments describing the morphogenesis of the pancreas and the epithelio-mesenchymal interactions that are instrumental for proper pancreas development. Recent findings suggest that follistatin and fibroblast growth factors represent some of these key mesenchymal factors that actively promote at least pancreatic exocrine development. The true endodermal origin of the pancreatic endocrine cells became evident by experiments performed by the groups of LeDouarin and Rutter in the 1970s. The newly acquired insights regarding the specification of pancreatic endocrine cells as controlled by the notch signaling pathway (i.e., similar to the mechanisms by which neurons are specified during neurogenesis) have provided a novel understanding of the long acknowledged similarities between neurons and the pancreatic endocrine cells. Last, the identification of a number of distinct transcription factors operating at various levels of pancreatic development and in different cell types has provided useful information both on pancreas development and on various pancreatic disorders such as diabetes. Interestingly, four of the hitherto defined five different maturity-onset diabetes of the young (MODY) genes correspond to transcription factors, and, in addition, several transcription factors have also been linked to type 2 diabetes. Diabetes 50 (Suppl. 1): S5-S9, 2001 T he pancreas comprises endocrine, exocrine, and ductal cell types that collectively synthesize and secrete hormones and enzymes required for nutritional balance. Each of these distinct pancreatic cell types are derived from endodermal cells of the upper duodenal region of the foregut (1,2), and the development of the pancreas begins with the dorsal and ventral protrusion of a region of the primitive gut epithelium (3-5). The early steps that control the commitment of a region of localized gut epithelium to a pancreatic fate and the mechanism underlying the specification of the different pancreatic cell types are, however, not well understood. In addition, it remains unclear how the initially separate programs of dorsal and ventral pancreatic bud development are coordinated to produce a convergent developmental program.Several homeodomain and basic helix-loop-helix (bHLH) transcription factors, notably Isl1, Nkx2.2, Pax4, Pax6, and NeuroD/␤2, have been shown to exert important functions in the control of pancreatic endocrine cell differentiation (3-5). These factors are expressed at early stages of pancreas development, but in their absence, the initial steps of pancreatic development proceed normally, resulting only later in perturbation of the differentiation of pancreatic endocrine cell types (3-5). In contrast to the bH...

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“…The pancreatic epithelium gives rise to exocrine cells, pancreatic ductal cells, and four different types of endocrine cells, which produce the hormones insulin, glucagon, somatostatin, and pancreatic polypeptide (PP), respectively. Proliferation of the pancreatic epithelium depends on signals from the surrounding mesenchyme (Golosow and Grobstein, 1962;Wessells and Cohen, 1967). In the absence of mesenchyme, growth and morphogenesis of the pancreatic buds are severely impaired and the epithelium undergoes a "default" endocrine differentiation at the expense of exocrine acinar formation (Gittes et al, 1996;Miralles et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Expression of Sox transcription factors in the developing mouse pancreas

Lioubinski¹,

Müller²,

Wegner

et al. 2003

Developmental Dynamics

113

128

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Previous work has identified members of the homeodomain and basic helix-loop-helix families of transcription factors as critical determinants of mammalian pancreatic development. Here, we describe the identification of HMG-box transcription factors of the Sox gene family in the mouse pancreas. We detected transcripts for Sox11, Sox4, Sox13, Sox5, Sox9, Sox8, Sox10, Sox7, Sox17, Sox18, Sox15, and Sox30 in embryonic pancreas and found Sox4, Sox9, and Sox13 in adult pancreatic islets. Expression of seven of these Sox factors was studied in more detail by in situ hybridization from the stage of early pancreatic outgrowth to birth. Expression of Sox11 was found in the mesenchyme surrounding the pancreatic buds, whereas Sox4 and Sox9 were confined to the pancreatic epithelium and later to islets. Sox13 and L-Sox5 showed expression in most of the pancreatic epithelial cells between embryonic days 12.5 and 14.5. Sox8 and Sox10 were detected in a thin layer of cells surrounding the islets. The expression patterns of Sox genes in the embryonic pancreas suggest that they could have important and possibly redundant functions in pancreas development. Developmental Dynamics 227:402-408, 2003.

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Early pancreas organogenesis: Morphogenesis, tissue interactions, and mass effects

Cited by 295 publications

References 30 publications

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

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

Developmental biology of the pancreas.

Expression of Sox transcription factors in the developing mouse pancreas

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