Cdx4 is required in the endoderm to localize the pancreas and limitβ-cell number

Kinkel, Mary D.; Eames, Stefani C.; Alonzo, Martha R.; Prince, Victoria

doi:10.1242/dev.010660

Cited by 46 publications

(45 citation statements)

References 52 publications

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“…Here we show that the anterior extent of the pancreas is restricted by endodermally expressed Cyp26a1, which degrades RA in the endoderm and thus restricts the anterior extent of the pancreas. We previously showed that the endodermally expressed Cdx4 transcription factor limits RA signaling in the posterior endoderm, thus setting the posterior limit of the pancreas (1). Together, these studies suggest a model in which foregut endoderm is patterned by the combined action of mesodermderived RA and endodermal factors that restrict its effect.…”

Section: Discussionmentioning

confidence: 85%

“…4D). Although a single embryo showed an AP expansion of the insulin-positive domain, the cells were sparse and scattered, suggesting a developmental delay rather than altered pancreas location (1). Together, these data suggest that Cyp26a1 activity in paraxial mesoderm does not influence pancreatic domain size or location.…”

Section: Cell Transplantation Demonstrates That Cyp26a1 Functions Withinmentioning

confidence: 79%

“…Morpholinos for cyp26a1 (13), cyp26b1 (15), and cyp26c1 (15) were used at 5 ng/ L. Cell transplantation was performed as described (7); in situ hybridization was performed as described (31), using the following probes: aldh1a2 (32), cebpa (33), cyp26a1 (12), cyp26b1 (14), cyp26c1 (34), foxa2 (35), glucagon (36), hhex (37), insulin (38), islet1 (39), myod1 (40), pdx1 (41), and somatostatin 2 (36). Myosin antibody staining was performed as previously described (1).…”

Section: Methodsmentioning

confidence: 99%

“…Endoderm regionalization is inf luenced by a variety of signals from the adjacent mesoderm, including retinoic acid (RA) (reviewed in ref. 1). When zebrafish RA signaling is disrupted pharmacologically or genetically, no pancreas develops (2).…”

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confidence: 99%

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Cyp26 enzymes function in endoderm to regulate pancreatic field size

Kinkel¹,

Sefton²,

Kikuchi

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The control of organ size and position relies, at least in part, upon appropriate regulation of the signals that specify organ progenitor fields. Pancreatic cell fates are specified by retinoic acid (RA), and proper size and localization of the pancreatic field are dependent on tight control of RA signaling. Here we show that the RAdegrading Cyp26 enzymes play a critical role in defining the normal anterior limit of the pancreatic field. Disruption of Cyp26 function causes a dramatic expansion of pancreatic cell types toward the anterior of the embryo. The cyp26a1 gene is expressed in the anterior trunk endoderm at developmental stages when RA is signaling to specify pancreas, and analysis of cyp26a1/giraffe (gir) mutant zebrafish embryos confirms that cyp26a1 plays the primary role in setting the anterior limit of the pancreas. Analysis of the gir mutants further reveals that cyp26b1 and cyp26c1 function redundantly to partially compensate for loss of Cyp26a1 function. We used cell transplantation to determine that Cyp26a1 functions directly in endoderm to modulate RA signaling and limit the pancreatic field. Taken together with our finding that endodermal expression of cyp26 genes is subject to positive regulation by RA, our data reveal a feedback loop within the endoderm. Such feedback can maintain consistent levels of RA signaling, despite environmental fluctuations in RA concentration, thus ensuring a consistent size and location of the pancreatic field.␤-cell ͉ insulin ͉ retinoic acid ͉ zebrafish

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Section: Discussionmentioning

confidence: 85%

Section: Cell Transplantation Demonstrates That Cyp26a1 Functions Withinmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Cyp26 enzymes function in endoderm to regulate pancreatic field size

Kinkel¹,

Sefton²,

Kikuchi

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…In contrast, the anterior boundary is restricted by Cyp26a1, which metabolizes RA and depletes its activity in the anterior endoderm, thus establishing the proper pancreatic field/size (Kinkel et al, 2008. The level of conservation in determining pancreatic boundary establishment by Cdx4 and Cyp26a1 across vertebrate species has not been determined.…”

Section: Figmentioning

confidence: 99%

Pancreas organogenesis: From bud to plexus to gland

Pan

Wright

2011

Developmental Dynamics

524

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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Effects of Precaudal Elongation on Visceral Topography in a Basal Clade of Ray‐Finned Fishes

Ward

Kley

2011

The Anatomical Record

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Elongate body forms have evolved numerous times independently within Vertebrata. Such body forms have evolved in large part via changes to the vertebral column, either through addition or lengthening of vertebrae. Previous studies have shown that body elongation in fishes has evolved most frequently through the addition of caudal vertebrae. In contrast, however, body elongation in Polypteriformes, a basal clade of ray-finned fishes (Actinopterygii), has evolved through the addition of precaudal vertebrae; one genus, Erpetoichthys, has approximately twice as many precaudal vertebrae as do members of its sister genus, Polypterus. Thus, polypteriform fishes provide an excellent opportunity to study the effects of precaudal elongation on the gross morphology and organization of visceral organs contained within the body cavity. In this study, we document the anteroposterior positions of most major visceral organs in representative species of both genera (E. calabaricus and P. palmas), relative to both vertebral number and percent pre-anal length. We found that, whereas the positions of the anterior and posterior borders of the visceral organs relative to percent pre-anal length were generally similar between the two species, most visceral organs were positioned further posteriorly in E. calabaricus than in P. palmas with respect to vertebral number. Based on previous determinations of the molecular control of anteroposterior patterning of the visceral organs, we discuss which possible changes in gene expression may have led to the anatomical modifications seen in the visceral morphology of Erpetoichthys. Anat Rec, 295:289-297, 2012. V V C 2011 Wiley Periodicals, Inc.

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Cdx4 is required in the endoderm to localize the pancreas and limitβ-cell number

Cited by 46 publications

References 52 publications

Cyp26 enzymes function in endoderm to regulate pancreatic field size

Cyp26 enzymes function in endoderm to regulate pancreatic field size

Pancreas organogenesis: From bud to plexus to gland

Effects of Precaudal Elongation on Visceral Topography in a Basal Clade of Ray‐Finned Fishes

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