Graded Hedgehog and Fibroblast Growth Factor Signaling Independently Regulate Pituitary Cell Fates and Help Establish the Pars Distalis and Pars Intermedia of the Zebrafish Adenohypophysis

Guner, Burcu; Ozacar, A. Tuba; Thomas, Jeanne E.; Karlstrom, Rolf O.

doi:10.1210/en.2008-0315

Cited by 27 publications

(18 citation statements)

References 68 publications

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“…Pax7 is another member of the Pax family and expressed in developing muscle and brain, and Pax7 expression is maintained after birth in both tissues 51–54. Here, we show that Pax7 is expressed in adult mouse pituitary gland, consistent with a previous report that Pax7 is expressed in the precursors of the pituitary gland of the zebrafish embryo 55. Taken together with our detection of Pax7 in the macaque pituitary, Pax7 expression in the pituitary gland appears to be well conserved in the macaque and human pituitary as a precursor to a corticotroph/melanotroph population in the intermediate lobe (Suppl.…”

Section: Discussionsupporting

confidence: 92%

A Postnatal Pax7+ Progenitor Gives Rise to Pituitary Adenomas

Hosoyama¹,

Nishijo²,

Garcia³

et al. 2010

Genes & Cancer

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Pituitary adenomas are classified into functioning and nonfunctioning (silent) tumors on the basis of hormone secretion. However, the mechanism of tumorigenesis and the cell of origin for pituitary adenoma subtypes remain to be elucidated. Employing a tamoxifen-inducible mouse model, we demonstrate that a novel postnatal Pax7+ progenitor cell population in the pituitary gland gives rise to silent corticotroph macro-adenomas when the retinoblastoma tumor suppressor is conditionally deleted. While Pax transcriptional factors are critical for embryonic patterning as well as postnatal stem cell renewal for many organs, we have discovered that Pax7 marks a restricted cell population in the postnatal pituitary intermediate lobe. This Pax7+ early progenitor cell population is overlapping but ontologically downstream of the Nestin+ pituitary stem cell population, yet upstream of another newly discovered Myf6+ late progenitor cell population. Interestingly, the Pax7+ progenitor cell population is evolutionarily conserved in primates and humans, and Pax7 expression is maintained not only in murine tumors but also in human functioning and silent corticotropinomas. Taken together, our results strongly suggest that human silent corticotroph adenomas may in fact arise from a Pax7 lineage of the intermediate lobe, a region of the human pituitary bearing closer scientific interest as a reservoir of pituitary progenitor cells.

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Section: Discussionsupporting

confidence: 92%

A Postnatal Pax7+ Progenitor Gives Rise to Pituitary Adenomas

Hosoyama¹,

Nishijo²,

Garcia³

et al. 2010

Genes & Cancer

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“…S2A,B, in the supplementary material; data not shown). Our previous work showed that Hh dosage regulates endocrine cell differentiation, with Prolactin-(Prl), Adrenocorticotropic hormone-(Acth; Pomca -Zebrafish Information Network) and Growth hormone-(Gh; Gh1 -Zebrafish Information Network) secreting cells being the most sensitive to reduced Hh signaling levels (Guner et al, 2008). Consistent with a mild loss of Hh signaling in uml(boc) mutants, gh-expressing cells were absent, acth-and prl-expressing cells…”

Section: Boc Function Is Necessary For Pituitary Development Early Mmentioning

confidence: 82%

“…S2 in the supplementary material) (Guner et al, 2008;Devine et al, 2009), suggest a novel role for Boc in Hh-mediated pituitary patterning. Low-level boc expression was detected in the placode region prior to 24 hpf, however boc expression was not seen in the placode by 36 hpf.…”

Section: Boc and Pituitary Developmentmentioning

confidence: 99%

brother of cdo (umleitung) is cell-autonomously required for Hedgehog-mediated ventral CNS patterning in the zebrafish

et al. 2011

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SUMMARYThe transmembrane protein Brother of Cdo (Boc) has been implicated in Shh-mediated commissural axon guidance, and can both positively and negatively regulate Hedgehog (Hh) target gene transcription, however, little is known about in vivo requirements for Boc during vertebrate embryogenesis. The zebrafish umleitung (uml ty54 ) mutant was identified by defects in retinotectal axon projections. Here, we show that the uml locus encodes Boc and that Boc function is cell-autonomously required for Hh-mediated neural patterning. Our phenotypic analysis suggests that Boc is required as a positive regulator of Hh signaling in the spinal cord, hypothalamus, pituitary, somites and upper jaw, but that Boc might negatively regulate Hh signals in the lower jaw. This study reveals a role for Boc in ventral CNS cells that receive high levels of Hh and uncovers previously unknown roles for Boc in vertebrate embryogenesis.

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“…2B). nxk2.2a expression is induced by Hh signaling and pax3a expression is repressed by Hh (Guner et al, 2008; Liem et al, 1995). The polarity of the vertebrate neural tube is established by a gradient of Shh (Briscoe and Ericson, 1999), and we wondered if Rest knockdown enhanced expression of other Hh target genes within the developing neural tube.…”

Section: Resultsmentioning

confidence: 99%

The transcriptional repressor REST/NRSF modulates hedgehog signaling

Gates

Mentzer

Karlstrom

et al. 2010

Developmental Biology

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The spatial and temporal control of gene expression is key to generation of specific cellular fates during development. Studies of the transcriptional repressor REST/NRSF (RE1 Silencing Transcription Factor or Neural Restrictive Silencing Factor) have provided important insight into the role that epigenetic modifications play in differential gene expression. However, the precise function of REST during embryonic development is not well understood. We have discovered a novel interaction between zebrafish Rest and the Hedgehog (Hh) signaling pathway. We observed that Rest knockdown enhances or represses Hh signaling in a context-dependant manner. In wild-type embryos and embryos with elevated Hh signaling, Rest knockdown augments transcription of Hh target genes. Conversely, in contexts where Hh signaling is diminished, Rest knockdown has the opposite effect and Hh target gene expression is further attenuated. Epistatic analysis revealed that Rest interacts with the Hh pathway at a step downstream of Smo. Furthermore, we present evidence implicating the bifunctional, Hh signaling component Gli2a as key to the Rest modulation of the Hh response. The role of Rest as a regulator of Hh signaling has broad implications for many developmental contexts where REST and Hh signaling act.

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Graded Hedgehog and Fibroblast Growth Factor Signaling Independently Regulate Pituitary Cell Fates and Help Establish the Pars Distalis and Pars Intermedia of the Zebrafish Adenohypophysis

Cited by 27 publications

References 68 publications

A Postnatal Pax7+ Progenitor Gives Rise to Pituitary Adenomas

A Postnatal Pax7+ Progenitor Gives Rise to Pituitary Adenomas

brother of cdo (umleitung) is cell-autonomously required for Hedgehog-mediated ventral CNS patterning in the zebrafish

The transcriptional repressor REST/NRSF modulates hedgehog signaling

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