The role of phospholipase C gamma 1 in primitive hematopoiesis during zebrafish development

C.H., Alvin; Liang, Raymond; Leung, Anskar Y. H.

doi:10.1016/j.exphem.2006.11.010

Cited by 15 publications

(16 citation statements)

References 21 publications

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“…In cancer model, survivin expression was regulated by vascular endothelial growth factor (VEGF) in a phosphatidylinositol 3-kinase-dependent fashion. 24 In the zebrafish embryos, despite the observations that VEGF inhibitor significantly reduced primitive hematopoiesis 25 and sur2 mRNA expression (data not shown), the phenotype could not be rescued by either WT or phosphorylation mimetic forms of sur2 mRNA (data not shown). Alternative regulatory signals for sur2 expression in zebrafish embryos remain to be further elucidated.…”

Section: Discussionmentioning

confidence: 85%

The role of survivin2 in primitive hematopoiesis during zebrafish development

Chung

Liang

et al. 2009

Leukemia

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Section: Discussionmentioning

confidence: 85%

The role of survivin2 in primitive hematopoiesis during zebrafish development

Chung

Liang

et al. 2009

Leukemia

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“…The importance of other elements of the phosphoinositide signaling cascade such as phospholipase C-mediated PtdIns(4,5)P 2 breakdown and InsP 3 production was shown in the very early fourcell stage development (Ashworth et al, 2007) as well as in dorsoventral patterning and Wnt signaling (Westfall et al, 2003). PLC1 was also found to be important in zebrafish primitive hematopoiesis (Ma et al, 2007) and vasculogenesis (Lawson et al, 2003). However, it will be important to determine whether kinase-dead versions of Pi4ka can rescue the pectoral-fin defect and whether alternative induction or activation of the putative downstream signaling molecules such as Akt and MKP3 can rescue this phenotype.…”

Section: Discussionmentioning

confidence: 99%

Crucial role of phosphatidylinositol 4-kinase IIIα in development of zebrafish pectoral fin is linked to phosphoinositide 3-kinase and FGF signaling

Blake

Chitnis

et al. 2009

Journal of Cell Science

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Phosphatidylinositol 4-kinases (PI4Ks) catalyze the first committed step in the synthesis of phosphoinositides, important lipid regulators of signaling and trafficking pathways. Here we cloned Pik4a, one of the zebrafish PI4K enzymes, and studied its role(s) in vertebrate development using morpholino oligonucleotide-based gene silencing in zebrafish. Downregulation of Pik4a led to multiple developmental abnormalities, affecting the brain, heart, trunk and most prominently causing loss of pectoral fins. Strikingly similar defects were caused by treatment of the developing embryos with the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. To investigate the cause of the pectoral fin developmental defect, we focused on fibroblast growth factor (FGF) signaling pathways because vertebrate limb development requires the concerted action of a series of FGF ligands. Using in situ hybridization, the pectoral fin defect was traced to disruption of the early FGF signaling loops that are crucial for the establishment of the sharp signaling center formed by the apical ectodermal ridge and the underlying mesenchyme. This, in turn caused a prominent loss of the induction of one of the mitogen-activated protein kinase (MAPK) phosphatases, Mkp3, an essential intermediate in vertebrate limb development. These changes were associated with impaired proliferation in the developing fin bud due to a loss of balance between the MAPK and PI3K branch of FGF-initiated signals. Our results identify Pik4a as an upstream partner of PI3Ks in the signaling cascade orchestrated by FGF receptors with a prominent role in forelimb development.

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“…So far, a role of Plcγ1 signaling has been only described in primitive erythropoiesis of the yolk sac in mouse and zebrafish. 11,14 Primitive erythropoiesis is not exclusively dependent on Epo, 38,39 whereas fetal liver and adult erythropoiesis is critically regulated by Epo-EpoR signaling. 4,24 As Plcγ1 is activated downstream of EpoR-Jak2 in I/11 proerythroblasts, we focused on its role in terminal erythroid differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…13 Knockdown of Plcγ1 in zebrafish embryos confirmed a role for Plcγ1 in early erythroid 1 differentiation. 14 All these results point to a major role for Plcγ1 in regulation of erythroid development. However, as outlined above, Stat5 is generally considered to be the 'canonical' major driver downstream of EpoR-Jak2-mediated erythropoiesis.…”

mentioning

confidence: 91%

Epo-induced erythroid maturation is dependent on Plcγ1 signaling

et al. 2014

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Erythropoiesis is a tightly regulated process. Development of red blood cells occurs through differentiation of hematopoietic stem cells (HSCs) into more committed progenitors and finally into erythrocytes. Binding of erythropoietin (Epo) to its receptor (EpoR) is required for erythropoiesis as it promotes survival and late maturation of erythroid progenitors. In vivo and in vitro studies have highlighted the requirement of EpoR signaling through Janus kinase 2 (Jak2) tyrosine kinase and Stat5a/b as a central pathway. Here, we demonstrate that phospholipase C gamma 1 (Plcγ1) is activated downstream of EpoR-Jak2 independently of Stat5. Plcγ1-deficient pro-erythroblasts and erythroid progenitors exhibited strong impairment in differentiation and colony-forming potential. In vivo, suppression of Plcγ1 in immunophenotypically defined HSCs (Lin − Sca1 + KIT + CD48 − CD150 + ) severely reduced erythroid development. To identify Plcγ1 effector molecules involved in regulation of erythroid differentiation, we assessed changes occurring at the global transcriptional and DNA methylation level after inactivation of Plcγ1. The top common downstream effector was H2afy2, which encodes for the histone variant macroH2A2 (mH2A2). Inactivation of mH2A2 expression recapitulated the effects of Plcγ1 depletion on erythroid maturation. Taken together, our findings identify Plcγ1 and its downstream target mH2A2, as a 'non-canonical' Epo signaling pathway essential for erythroid differentiation.

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The role of phospholipase C gamma 1 in primitive hematopoiesis during zebrafish development

Cited by 15 publications

References 21 publications

The role of survivin2 in primitive hematopoiesis during zebrafish development

The role of survivin2 in primitive hematopoiesis during zebrafish development

Crucial role of phosphatidylinositol 4-kinase IIIα in development of zebrafish pectoral fin is linked to phosphoinositide 3-kinase and FGF signaling

Epo-induced erythroid maturation is dependent on Plcγ1 signaling

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