Role of IGF signaling in catch-up growth and accelerated temporal development in zebrafish embryos in response to oxygen availability

Kamei, Hiroyasu; Ding, Yonghe; Kajimura, Shingo; Wells, Michael B.; Chiang, Peter K.; Duan, Cunming

doi:10.1242/dev.056853

Cited by 77 publications

(64 citation statements)

References 41 publications

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“…For example, IGF signaling is increased and has a role in the exercise-induced skeletal muscle hypertrophy in mammals, 51 in fin regeneration upon amputation in zebrafish, 52 and in catch-up growth during re-oxygenation in zebrafish. 53 The results of the present study, along with those mentioned above, suggest that co-option of the ubiquitous IGF signaling pathway in regulating plastic changes of specific tissues in response to environmental factors may be a common theme. .…”

Section: Discussionsupporting

confidence: 67%

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

et al. 2013

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Calcium deficiency causes abnormal colonic growth and increases colon cancer risk with poorly understood mechanisms. Here we elucidate a novel signaling mechanism underlying the Ca 2 þ deficiency-induced epithelial proliferation using a unique animal model. The zebrafish larval yolk sac skin contains a group of Ca 2 þ -transporting epithelial cells known as ionocytes. Their number and density increases dramatically when acclimated to low [Ca 2 þ ] environments. BrdU pulse-labeling experiments suggest that low [Ca 2 þ ] stimulates pre-existing ionocytes to re-enter the cell cycle. Low [Ca 2 þ ] treatment results in a robust and sustained activation of IGF1R-PI3K-Akt signaling in these cells exclusively. These ionocytes specifically express Igfbp5a, a high-affinity and specific binding protein for insulin-like growth factors (IGFs) and the Ca 2 þ -selective channel Trpv5/6. Inhibition or knockdown of Igfbp5a, IGF1 receptor, PI3K, and Akt attenuates low [Ca 2 þ ]-induced ionocyte proliferation. The role of Trpv5/6 was investigated using a genetic mutant, targeted knockdown, and pharmacological inhibition. Loss-of-Trpv5/6 function or expression results in elevated pAkt levels and increased ionocyte proliferation under normal [Ca 2 þ ]. These increases are eliminated in the presence of an IGF1R inhibitor, suggesting that Trpv5/6 represses IGF1R-PI3K-Akt signaling under normal [Ca 2 þ ]. Intriguingly, blockade of Trpv5/6 activity inhibits the low [Ca 2 þ ]-induced activation of Akt. Mechanistic analyses reveal that the low [Ca 2 þ ]-induced IGF signaling is mediated through Trpv5/6-associated membrane depolarization. Low extracellular [Ca 2 þ ] results in a similar amplification of IGF-induced PI3K-PDK1-Akt signaling in human colon cancer cells in a TRPV6-dependent manner. These results uncover a novel and evolutionarily conserved signaling mechanism that contributes to the abnormal epithelial proliferation associated with Ca 2 þ deficiency.

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Section: Discussionsupporting

confidence: 67%

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

et al. 2013

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“…Phenylthiourea (0.2 mM) was added to prevent pigmentation. Tg(hsp70:dnIGF1R-GFP) and Tg(hsp70:GFP) transgenic lines, which express a dominant-negative form of IGF1R-GFP (dnIGF1R-GFP) or GFP under the control of the zebrafish hsp70 promoter, were generated and maintained as reported (Kamei et al, 2011). The generation of the Tg(GnRH3:EGFP) transgenic line that expresses EGFP in GnRH3 neurons has been reported previously (Abraham et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

“…Approximately 60 embryos for each group were dechorionated, deyolked, homogenized, centrifuged, and subjected to immunobloting analysis. For phospho-IGF1R and FGFR1, equal amounts of proteins were subjected to immunoprecipitation using the G416 phosphotyrosine antibody and followed by Western immunoblotting as described previously (Kamei et al, 2011).…”

Section: Methodsmentioning

confidence: 99%

“…Two transgenic zebrafish lines, Tg(hsp70:dnIGF1R-GFP) and Tg(hsp70:GFP), that express a dominant-negative form of the zebrafish IGF1Ra or GFP alone under the control of the heat shock-inducible hsp70 promoter (Kamei et al, 2011) were used to investigate the role of IGF signaling in GnRH neuron development. Fluorescence microscopy indicated robust expression of dnIGF1R-GFP or GFP expression after the HS treatment (1 h at 37°C) (Fig.…”

Section: Genetic and Pharmacological Blockade Of Igf1r Signaling In Zmentioning

confidence: 99%

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Regulation of Temporal and Spatial Organization of Newborn GnRH Neurons by IGF Signaling in Zebrafish

Onuma¹,

Ding²,

Abraham³

et al. 2011

J. Neurosci.

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When and how newborn neurons are organized to form a functional network in the developing brain remains poorly understood. An attractive model is the gonadotropin-releasing hormone (GnRH) neuron system, master regulator of the reproductive axis. Here we show that blockage of IGF signaling, a central growth-promoting signaling pathway, by the induced expression of a dominant-negative form of IGF1 receptor (IGF1R) or specific IGF1R inhibitors delayed the emergence of GnRH2 neurons in the midbrain and GnRH3 neurons in the olfactory bulb region. Blockage of IGF signaling also resulted in an abnormal appearance of GnRH3 neurons outside of the olfactory bulb region, although it did not change the locations of other olfactory neurons, GnRH2 neurons, or brain patterning. This IGF action is developmental stage-dependent because the blockade of IGF signaling in advanced embryos had no such effect. An application of phosphatidylinositol 3-kinase (PI3K) inhibitors phenocopied the IGF signaling deficient embryos, whereas the MAPK inhibitors had no effect, suggesting that this IGF action is mediated through the PI3K pathway. Real-time in vivo imaging studies revealed that the ectopic GnRH3 neurons emerged at the same time as the normal GnRH3 neurons in IGF-deficient embryos. Further experiments suggest that IGF signaling affects the spatial distribution of newborn GnRH3 neurons by influencing neural crest cell migration and/or differentiation. These results suggest that the IGF-IGF1R-PI3K pathway regulates the precise temporal and spatial organization of GnRH neurons in zebrafish and provides new insights into the regulation of GnRH neuron development.

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“…Insulin-like growth factor 1 (IGF-1), a major regulator of growth and metabolism, has generated significant interest in the field (2). IGF-1 disruption has been implicated in aberrant growth and development of metabolic syndrome in both IUGR humans and animal models (3)(4)(5)(6). In particular, decreased IGF-1 have been observed in IUGR humans who ultimately develop metabolic syndrome as adults (7,8).…”

mentioning

confidence: 99%

IUGR prevents IGF-1 upregulation in juvenile male mice by perturbing postnatal IGF-1 chromatin remodeling

Fung

Yang

et al. 2015

Pediatr Res

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Background: Intrauterine growth restriction (IUGR) offspring with rapid catch-up growth are at increased risk for early obesity especially in males. Persistent insulin-like growth factor-1 (IGF-1) reduction is an important risk factor. Using a mouse model of maternal hypertension-induced IUGR, we examined IGF-1 levels, promoter DNA methylation, and histone H3 covalent modifications at birth (D1). We additionally investigated whether prenatal perturbations could reset at preadolescence (D21). Methods: IUGR was induced via maternal thromboxane A 2 -analog infusion in mice. results: IUGR uniformly decreased D1 IGF-1 mRNA and protein levels with reduced promoter 1 (P1) transcription and increased P1 DNA methylation. IUGR males also had increased H3K4ac at exon 5 and 3′ distal UTR. At D21, IUGR males continued to have decreased IGF-1 levels, originating from both P1 and P2 with reduced 1A variant. IUGR males also had decreased activation mark of H3K4me3 at P1 compared with sham males. In contrast, D21 IUGR females normalized their IGF-1 levels, in association with an increased activation mark of H3K4me3 at P1 compared with sham females. conclusion: IUGR uniformly affected D1 hepatic IGF-1 epigenetic modifications in both sexes. However, at preadolescence, IUGR males are unable to correct for the prenatal reduction possibly due to a more perturbed IGF-1 chromatin structure.i ntrauterine growth restriction (IUGR) predisposes offspring toward early-onset metabolic syndrome. This predisposition is particularly pertinent with rapid postnatal catch-up growth and affects males more than females (1). The molecular mechanisms underlying this sex-specific predisposition remain elusive. Insulin-like growth factor 1 (IGF-1), a major regulator of growth and metabolism, has generated significant interest in the field (2). IGF-1 disruption has been implicated in aberrant growth and development of metabolic syndrome in both IUGR humans and animal models (3-6). In particular, decreased IGF-1 have been observed in IUGR humans who ultimately develop metabolic syndrome as adults (7,8).The IGF-1 gene is an ideal candidate to examine IUGR's effects not only because of its growth and metabolic properties but because of its complex gene structure allowing for developmental-and tissue-specific expression. The majority of serum IGF-1 is synthesized from the liver (9). The IGF-1 gene is regulated by two alternative promoters, promoter P1 initiates transcription from exon 1 while promoter P2 from exon 2. P1 is active in fetal life, whereas P2 becomes upregulated at ~3 wk of life when growth hormone exerts its effects on the rodent IGF-1 gene (10). The rodent IGF-1 gene also has an alternatively spliced exon, with the A variant excluding exon 5 and the B variant includes exon 5. Both alternative promoter selection and alternative exon splicing require specific epigenetic modifications to direct transcriptional machinery for specific mRNA transcript generation (11,12).Given that prenatal insults are known to affect gene-specific DNA methylation a...

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Role of IGF signaling in catch-up growth and accelerated temporal development in zebrafish embryos in response to oxygen availability

Cited by 77 publications

References 41 publications

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

Regulation of Temporal and Spatial Organization of Newborn GnRH Neurons by IGF Signaling in Zebrafish

IUGR prevents IGF-1 upregulation in juvenile male mice by perturbing postnatal IGF-1 chromatin remodeling

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