Fibroblast growth factor signaling is required for the proliferation and patterning of progenitor cells in the developing anterior pituitary

Norlin, Stefan; Nordström, Ulrika; Edlund, Thomas

doi:10.1016/s0925-4773(00)00393-2

Cited by 50 publications

(43 citation statements)

References 36 publications

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“…Several FGFs, including Fgf8, Fgf10 and Fgf18 are expressed in the developing ventral diencephalon around 9.5-10.5 dpc (Treier et al, 1998(Treier et al, , 2001, and loss-of-function mutants of FGF and FGFR2 demonstrate that FGF signalling is required for normal proliferation of RP progenitors and pituitary morphogenesis (De Moerlooze et al, 2000;Ohuchi et al, 2000). Ex vivo culture of RP tissue exposed to FGFs and FGF inhibitors has revealed a crucial function for the pathway in controlling both RP proliferation, and its downregulation is required for normal PIT1-cell lineage specification (Ericson et al, 1998;Norlin et al, 2000). Of note, transgenic ectopic expression of Fgf8 in the developing pituitary using a Cga (a-GSU) promoter results in pituitary hyperplasia and expansion of ACTH-expressing cells (corticotrophs and melanotrophs) with a concomitant severe loss of gonadotrophs, somatotrophs, thyrotrophs and gonadotrophs (Treier et al, 1998), a phenotype resembling our mouse models that activate the MAPK-ERK pathway.…”

Section: Discussionmentioning

confidence: 99%

MAPK pathway activation in the embryonic pituitary results in stem cell compartment expansion, differentiation defects and provides insights into the pathogenesis of papillary craniopharyngioma

et al. 2017

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Despite the importance of the RAS-RAF-MAPK pathway in normal physiology and disease of numerous organs, its role during pituitary development and tumourigenesis remains largely unknown. Here, we show that the over-activation of the MAPK pathway, through conditional expression of the gain-of-function alleles BrafV600E and KrasG12D in the developing mouse pituitary, results in severe hyperplasia and abnormal morphogenesis of the gland by the end of gestation. Cell-lineage commitment and terminal differentiation are disrupted, leading to a significant reduction in numbers of most of the hormone-producing cells before birth, with the exception of corticotrophs. Of note, Sox2 + stem cells and clonogenic potential are drastically increased in the mutant pituitaries. Finally, we reveal that papillary craniopharyngioma (PCP), a benign human pituitary tumour harbouring BRAF p.V600E also contains Sox2 + cells with sustained proliferative capacity and disrupted pituitary differentiation. Together, our data demonstrate a crucial function of the MAPK pathway in controlling the balance between proliferation and differentiation of Sox2 + cells and suggest that persistent proliferative capacity of Sox2 + cells may underlie the pathogenesis of PCP.

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Section: Discussionmentioning

confidence: 99%

MAPK pathway activation in the embryonic pituitary results in stem cell compartment expansion, differentiation defects and provides insights into the pathogenesis of papillary craniopharyngioma

et al. 2017

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“…Generation of cells with different hormone types is mostly instructed by a combination of localised extrinsic signals (BMP, Wnt, Shh, etc.) from neighbouring tissues, including ventral hypothalamus (Dasen and Rosenfeld, 2001;Ericson et al, 1998;Norlin et al, 2000;Rizzoti and LovellBadge, 2005;Potok et al, 2008). Among these endocrine cell types, differentiation of corticotropes (ACTH + ) is controlled in a relatively simple manner, via inhibition of the NotchHairy/Enhancer of Split pathway (Zhu et al, 2006;Kita et al, 2007).…”

Section: Adenohypophysis Generation In Culturementioning

confidence: 99%

In vitro organogenesis in three dimensions: self-organising stem cells

2012

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SummaryOrgan formation during embryogenesis is a complex process that involves various local cell-cell interactions at the molecular and mechanical levels. Despite this complexity, organogenesis can be modelled in vitro. In this article, we focus on two recent examples in which embryonic stem cells can self-organise into three-dimensional structures -the optic cup and the pituitary epithelium; and one case of self-organising adult stem cells -the gut epithelium. We summarise how these approaches have revealed intrinsic programs that drive locally autonomous modes of organogenesis and homeostasis. We also attempt to interpret the results of previous in vivo studies of retinal development in light of the self-organising nature of the retina.

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“…Bmp4 from the ventral diencephalon induces the formation and initial growth of Rathke's pouch, whereas expansion and maintenance of undifferentiated progenitors in the dorsal region of this tissue is mediated by members of the fibroblast growth factor family (Fgf8, Fgf10 and Fgf18) from the infundibulum (Ericson et al, 1998;Norlin et al, 2000;Treier et al, 1998;Treier et al, 2001). Infundibular Fgfs also counteract the activity of Bmp2 and Shh from the oral roof ectoderm, resulting in the patterning of Rathke's pouch along its dorsoventral axis.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Sox2-dependent activation of Shh in the ventral diencephalon by Tbx3 is required for formation of the neurohypophysis

et al. 2013

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SUMMARYTbx2 and Tbx3 are two highly related members of the T-box transcription factor gene family that regulate patterning and differentiation of a number of tissue rudiments in the mouse. Both genes are partially co-expressed in the ventral diencephalon and the infundibulum; however, a functional requirement in murine pituitary development has not been reported. Here, we show by genetic lineage tracing that Tbx2 + cells constitute the precursor population of the neurohypophysis. However, Tbx2 is dispensable for neurohypophysis development as revealed by normal formation of this organ in Tbx2-deficient mice. By contrast, loss of Tbx3 from the ventral diencephalon results in a failure to establish the Tbx2 + domain in this region, and a lack of evagination of the infundibulum and formation of the neurohypophysis. Rathke's pouch is severely hypoplastic, exhibits defects in dorsoventral patterning, and degenerates after E12.5. In Tbx3-deficient embryos, the ventral diencephalon is hyperproliferative and displays an abnormal cellular architecture, probably resulting from a failure to repress transcription of Shh. We further show that Tbx3 and Tbx2 repress Shh by sequestering the SRY box-containing transcription factor Sox2 away from a Shh forebrain enhancer (SBE2), thus preventing its activation. These data suggest that Tbx3 is required in the ventral diencephalon to establish a Shh -domain to allow formation of the infundibulum.

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Fibroblast growth factor signaling is required for the proliferation and patterning of progenitor cells in the developing anterior pituitary

Cited by 50 publications

References 36 publications

MAPK pathway activation in the embryonic pituitary results in stem cell compartment expansion, differentiation defects and provides insights into the pathogenesis of papillary craniopharyngioma

MAPK pathway activation in the embryonic pituitary results in stem cell compartment expansion, differentiation defects and provides insights into the pathogenesis of papillary craniopharyngioma

In vitro organogenesis in three dimensions: self-organising stem cells

Inhibition of Sox2-dependent activation of Shh in the ventral diencephalon by Tbx3 is required for formation of the neurohypophysis

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