Prox1 activity controls pancreas morphogenesis and participates in the production of “secondary transition” pancreatic endocrine cells

Wang, Junfeng; Kılıç, Gamze; Aydin, Müge; Burke, Zoë D.; Oliver, Guillermo; Sosa–Pineda, Beatriz

doi:10.1016/j.ydbio.2005.07.021

Cited by 116 publications

(105 citation statements)

References 41 publications

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“…By E13.5, it is expressed in Ngn3 + endocrine progenitors. Finally, from E15.5, Prox1 is specifically expressed in endocrine, ductal and centroacinar cells, while it is excluded from acinar cells (Wang et al, 2005).…”

Section: Prospero-related Homeobox Transcription Factor1 (Prox1)mentioning

confidence: 99%

Genes controlling pancreas ontogeny

Bonal¹,

Herrera²

2008

Int. J. Dev. Biol.

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The pancreas develops from two separate and independent endodermal primordia. The molecular events supporting the early morphological changes that give rise to the formation of the dorsal and ventral pancreatic buds result from coordinated responses to extrinsic and intrinsic signals. The extrinsic signals are involved in processes dictating whether progenitor cells remain as immature or as committed precursors. After specification, the sequential activation of transcription factors determines cell autonomously the commitment and differentiation of these progenitors. During pancreas development, the roles of extrinsic and intrinsic signals are variable, depending on the particular competence of each progenitor cell. We summarize in this review the main events, at the level of gene expression, which are involved in the early stages of pancreas development. KEY WORDS: islet, pancreas, progenitor, endocrine, development, beta cell The pancreas is an exocrine and endocrine gland of the digestive system (Fig. 1A). The exocrine part represents 95-99% of the total pancreatic mass. It consists of serous acini of highly polarized cells that produce digestive enzymes (amylase, lipase, phospholipase) as well as pro-enzymes (elastase, procarboxypeptidase, trypsinogen, pepsinogen, deoxyribonuclease, ribonuclease), which are stored in zymogen granules located in their apical pole (Fig. 1CD). Once secreted with water and bicarbonates into the lumen of the acinus, they become activated and forwarded through the ductal network to the duodenum, for the intestinal digestion of nutrients. The ductal tree begins within the acini with very small ducts lined by centroacinar cells, followed by intercalated, intralobular and finally interlobular ducts (Fig. 1CD).The endocrine pancreas is composed of islets of Langerhans scattered within the exocrine tissue, representing 1-5% of the pancreatic mass (Fig. 1BC). Adult islets are composed of different cell types characterized by the production of specific hormones: glucagon by α-cells, insulin by β-cells, somatostatin by δ-cells and pancreatic polypeptide by PP-cells. A rare fifth endocrine cell type, the ε-cell, secreting ghrelin, represents about 1% of the embryonic endocrine pancreas, but disappears after birth. In rodents, islets are composed of a central core of β-cells, which represent about 80% of all islet cells, surrounded by a mantle composed of the three other cell types (Fig. 1E). Insulin and glucagon control blood glucose levels, whereas PP and ghrelin are orexigenic hormones and somatostatin regulates the secretion of insulin, glucagon and PP.Int. J. Dev. Biol. 52: 823-835 (2008) doi: 10.1387/ijdb.072444cb Specification of pancreatic fateIn Mammals, the pancreatic differentiation program is induced in the foregut/midgut junction of the endoderm by factors released from the mesoderm at the 6-10 somites stage (6-10s) (Fig. 2). Initially, the dorsal endoderm is adjacent to the notochord, before the fusion of the two dorsal aortae at 12-20s (which corresponds to E8...

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Section: Prospero-related Homeobox Transcription Factor1 (Prox1)mentioning

confidence: 99%

Genes controlling pancreas ontogeny

Bonal¹,

Herrera²

2008

Int. J. Dev. Biol.

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“…Prox1 homologues have been identified in other vertebrates, including Xenopus, zebrafish, chicken, and human (Tomarev et al, 1996;Glasgow and Tomarev, 1998;Ny et al, 2005). In vertebrates, Prox1 is expressed in the developing neural retina, lens, cochlea, spinal cord, brain, skeletal muscle, heart, liver, pancreas, and in the endothelial cells that will give rise to the lymphatic vasculature (Oliver et al, 1993;Tomarev et al, 1996;Glasgow and Tomarev, 1998;Burke and Oliver, 2002;Wigle et al, 2002;Wang et al, 2005;Bermingham-McDonogh et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…In mice, functional inactivation of Prox1 demonstrated that this gene's activity is critical for the formation of a variety of organs and cell types, including the lens, retina, liver, pancreas, and lymphatic endothelial cells Sosa-Pineda et al, 2000;Hong et al, 2002;Dyer et al, 2003;Harvey et al, 2005;Wang et al, 2005). In Drosophila, prospero is a cell-fate determinant in the asymmetric divisions of neuroblasts (Doe et al, 1991;Vaessin et al, 1991) and is required to maintain the mitotic potential of glial cells (Griffiths and Hidalgo, 2004).…”

Section: Introductionmentioning

confidence: 99%

Prox1 expression patterns in the developing and adult murine brain

Lavado

Oliver

2006

Developmental Dynamics

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144

124

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Prox1, a homeobox gene related to the Drosophila gene prospero, is necessary for retina, lens, liver, pancreas, and lymphatics development. However, not much is yet known about Prox1 expression during central nervous system development. Here we provide a detailed analysis of Prox1 mRNA and protein expression during prenatal and postnatal murine brain development. Prenatally, Prox1 is expressed in the subventricular zone or in early differentiating regions of the brain. At these stages, Prox1 mRNA, but not Prox1 protein, was also detected in several regions of the prethalamus and hypothalamus. At an early postnatal stage, Prox1 expression is mainly detected in several nuclei of the thalamus, the cerebellum, and the hippocampus. In adulthood, Prox1 expression remains only in the hippocampus and cerebellum. These complex patterns of expression suggest that Prox1 activity is differentially required during brain development and adulthood. Developmental Dynamics 236:518 -524, 2007.

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“…These defects were attributed to a non-cell-autonomous function for Cdc42 in positioning initially multipotent progenitors within environments conducive for endocrine differentiation. Finally, tissue-specific inactivation of transcription factors expressed in the trunk-such as HNF6 (Pierreux et al 2006), Prox1 (Wang et al 2005;Westmoreland et al 2012), or HNF1b (De Vas et al 2015-results in epithelial malformations and concurrent deficits in endocrine differentiation. While these outcomes are interpreted largely on the basis of upstream transcriptional effects on Ngn3, they are consistent with the idea that misregulated epithelial morphology precludes efficient engagement of the endocrine differentiation program.…”

mentioning

confidence: 99%

Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche

2015

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In the mammalian pancreas, endocrine cells undergo lineage allocation upon emergence from a bipotent duct/endocrine progenitor pool, which resides in the "trunk epithelium." Major questions remain regarding how niche environments are organized within this epithelium to coordinate endocrine differentiation with programs of epithelial growth, maturation, and morphogenesis. We used EdU pulse-chase and tissue-reconstruction approaches to analyze how endocrine progenitors and their differentiating progeny are assembled within the trunk as it undergoes remodeling from an irregular plexus of tubules to form the eventual mature, branched ductal arbor. The bulk of endocrine progenitors is maintained in an epithelial "plexus state," which is a transient intermediate during epithelial maturation within which endocrine cell differentiation is continually robust and surprisingly long-lived. Within the plexus, local feedback effects derived from the differentiating and delaminating endocrine cells nonautonomously regulate the flux of endocrine cell birth as well as proliferative growth of the bipotent cell population using Notch-dependent and Notch-independent influences, respectively. These feedback effects in turn maintain the plexus state to ensure prolonged allocation of endocrine cells late into gestation. These findings begin to define a niche-like environment guiding the genesis of the endocrine pancreas and advance current models for how differentiation is coordinated with the growth and morphogenesis of the developing pancreatic epithelium.

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Prox1 activity controls pancreas morphogenesis and participates in the production of “secondary transition” pancreatic endocrine cells

Cited by 116 publications

References 41 publications

Genes controlling pancreas ontogeny

Genes controlling pancreas ontogeny

Prox1 expression patterns in the developing and adult murine brain

Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche

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