WNT signaling affects gene expression in the ventral diencephalon and pituitary gland growth

We examined the role of WNT signaling in pituitary development by characterizing the pituitary phenotype of three WNT knockout mice and assessing the expression of WNT pathway components. Wnt5a mutants have expanded domains of Fgf10 and bone morphogenetic protein expression in the ventral diencephalon and a reduced domain of LHX3 expression in Rathke's pouch. Wnt4 mutants have mildly reduced cell differentiation, reduced POU1F1 expression, and mild anterior lobe hypoplasia. Wnt4 , Wnt5a double mutants exhibit an additive pituitary phenotype of dysmorphology and mild hypoplasia. Wnt6 mutants have no obvious pituitary phenotype. We surveyed WNT expression and identified transcripts for numerous Wnts , Frizzleds , and downstream pathway members in the pituitary and ventral diencephalon. These findings support the emerging model that WNT signaling affects the pituitary gland via effects on ventral diencephalon signaling, and suggest additional Wnt genes that are worthy of functional studies. Developmental Dynamics 237:1006–1020, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58083/1/21511_ftp.pd

WNT5A signaling affects pituitary gland shape

Wnt signaling is important in organogenesis, and aberrant signaling in mature cells is associated with tumorigenesis. Several members of the Wnt family of signaling molecules are expressed in the developing pituitary gland. Wnt5a is expressed in the neuroectoderm that induces pituitary gland development and has been proposed to influence pituitary cell specification. We discovered that mice deficient in Wnt5a display abnormal morphology in the dorsal part of the developing pituitary. The expression of downstream effectors of the canonical Wnt pathway is not altered, and expression of genes in other signaling pathways such as Shh, Fgf8, Fgf10 and Fgfr2b is intact. Prop1 and Hesx1 are also important for normal shape of the pituitary primordium, but their expression is unaltered in the Wnt5a mutants. Specification of the hormone-producing cell types of the mature anterior pituitary gland occurs appropriately. This study suggests that the primary role of Wnt5a in the developing pituitary gland is in establishment of the shape of the gland

Runx1 expression defines a subpopulation of displaced amacrine cells in the developing mouse retina

AML1 Runx1 (Runx1) is a mammalian transcription factor that plays critical roles in regulating the differentiation of a number of different cell types. In the present study, we have utilized mice expressing -galactosidase ( -gal) under the control of the Runx1 promoter to characterize the spatiotemporal expression pattern of Runx1 during retinogenesis. Expression of -gal was first detected at embryonic day 13.5 in post-mitotic cells located in the inner retina and overlapped with expression of the early amacrine and ganglion cell marker protein Islet1. During subsequent developmental stages, the number of -gal-positive cells increased in a central-to-peripheral gradient until late embryogenesis but then decreased in the early post-natal retina. -gal-positive cells were located primarily in the ganglion cell layer by late embryonic early post-natal stages and were identified as a subpopulation of displaced amacrine cells by the continued expression of Islet1, as well as Pax6, and the coexpression of the amacrine cell subtype-specific markers choline acetyltransferase, calretinin and the 65-kDa isoform of glutamic acid decarboxylase. These findings identify Runx1 as a novel marker for a restricted amacrine cell subtype and suggest a role for this gene in regulating the post-mitotic development of these cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65442/1/j.1471-4159.2005.03336.x.pd

Identification of members of the Wnt signaling pathway in the embryonic pituitary gland

Prop1 is one of several transcription factors important for the development of the pituitary gland. Downstream targets of PROP1 and other critical pituitary transcription factors remain largely unknown. We have generated a partial expression profile of the developing pituitary gland containing over 350 transcripts, using cDNA subtractive hybridization between Prop1 df/df and wild-type embryonic pituitary gland primordia. Numerous classes of genes including transcription factors, membrane associated molecules, and cell cycle regulators were identified in this study. Of the transcripts, 34% do not have sequence similarity to known genes, but are similar to ESTs, and 4% represent novel sequences. Pituitary gland expression of a number of clones was verified using in situ hybridization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42122/1/335-12-11-843_10120843.pd

Genetics, Gene Expression and Bioinformatics of the Pituitary Gland

Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown etiology. These studies reveal critical roles for Wnt signalling pathways including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic proteins antagonists, and targets of notch signalling. Current studies are investigating roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers

Nonresonant central exclusive production of charged-hadron pairs in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe central exclusive production of charged-hadron pairs in pp collisions at a centre-of-mass energy of 13\TeV is examined, based on data collected in a special high-$\beta^*$ run of the LHC. The nonresonant continuum processes are studied with the invariant mass of the centrally produced two-pion system in the resonance-free region, $m_{\pi^+\pi^-}$$\lt$ 0.7 GeV or $m_{\pi^+\pi^-}$$\gt$ 1.8 GeV. Differential cross sections as functions of the azimuthal angle between the surviving protons, squared exchanged four-momenta, and $m_{\pi^+\pi^-}$ are measured in a wide region of scattered proton transverse momenta, between 0.2 and 0.8 GeV, and for pion rapidities $\lvert y\rvert$$\lt$ 2. A rich structure of interactions related to double-pomeron exchange is observed. A parabolic minimum in the distribution of the two-proton azimuthal angle is observed for the first time. It can be interpreted as an effect of additional pomeron exchanges between the protons from the interference between the bare and the rescattered amplitudes. After model tuning, various physical quantities are determined that are related to the pomeron cross section, proton-pomeron and meson-pomeron form factors, pomeron trajectory and intercept, and coefficients of diffractive eigenstates of the proton

Nonresonant central exclusive production of charged-hadron pairs in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe central exclusive production of charged-hadron pairs in pp collisions at a centre-of-mass energy of 13\TeV is examined, based on data collected in a special high-$\beta^*$ run of the LHC. The nonresonant continuum processes are studied with the invariant mass of the centrally produced two-pion system in the resonance-free region, $m_{\pi^+\pi^-}$$\lt$ 0.7 GeV or $m_{\pi^+\pi^-}$$\gt$ 1.8 GeV. Differential cross sections as functions of the azimuthal angle between the surviving protons, squared exchanged four-momenta, and $m_{\pi^+\pi^-}$ are measured in a wide region of scattered proton transverse momenta, between 0.2 and 0.8 GeV, and for pion rapidities $\lvert y\rvert$$\lt$ 2. A rich structure of interactions related to double-pomeron exchange is observed. A parabolic minimum in the distribution of the two-proton azimuthal angle is observed for the first time. It can be interpreted as an effect of additional pomeron exchanges between the protons from the interference between the bare and the rescattered amplitudes. After model tuning, various physical quantities are determined that are related to the pomeron cross section, proton-pomeron and meson-pomeron form factors, pomeron trajectory and intercept, and coefficients of diffractive eigenstates of the proton

Nonresonant central exclusive production of charged-hadron pairs in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe central exclusive production of charged-hadron pairs in pp collisions at a centre-of-mass energy of 13\TeV is examined, based on data collected in a special high-$\beta^*$ run of the LHC. The nonresonant continuum processes are studied with the invariant mass of the centrally produced two-pion system in the resonance-free region, $m_{\pi^+\pi^-}$$\lt$ 0.7 GeV or $m_{\pi^+\pi^-}$$\gt$ 1.8 GeV. Differential cross sections as functions of the azimuthal angle between the surviving protons, squared exchanged four-momenta, and $m_{\pi^+\pi^-}$ are measured in a wide region of scattered proton transverse momenta, between 0.2 and 0.8 GeV, and for pion rapidities $\lvert y\rvert$$\lt$ 2. A rich structure of interactions related to double-pomeron exchange is observed. A parabolic minimum in the distribution of the two-proton azimuthal angle is observed for the first time. It can be interpreted as an effect of additional pomeron exchanges between the protons from the interference between the bare and the rescattered amplitudes. After model tuning, various physical quantities are determined that are related to the pomeron cross section, proton-pomeron and meson-pomeron form factors, pomeron trajectory and intercept, and coefficients of diffractive eigenstates of the proton