Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein specification in vertebrates

Chun, Chang Zoon; Kaur, Sukhbir; Samant, Ganesh V.; Pramanik, Kallal; Garnaas, Maija K.; Li, Keguo; Field, Lyndsay; Mukhopadhyay, Debabrata; Ramchandran, Ramani

doi:10.1182/blood-2008-06-162156

Cited by 30 publications

(45 citation statements)

References 17 publications

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“…As shown previously, 12 Figure 3M) shows that 60% to 80% of snrk-1 mRNA-injected embryos showed increased etsrp staining along both axes of the embryo, 40% to 50% of dusp-5 mRNA-injected embryos showed increased etsrp along the shorter axis but decreased etsrp along the longer axis, and a majority (80%-100%) of double mRNA-injected embryos displayed increased etsrp Figure S2E) and snrk-1 ( Figure S2G) mRNA-injected embryos, this migration pattern is affected. In snrk-1 mRNAinjected embryos (Figure S2G), the overall extent of flk staining is increased, suggesting that ectopic induction of flk ϩ cells occurs.…”

Section: Ectopic Induction Of Etsrp ؉ Angioblasts By Snrk-1 Is Blockesupporting

confidence: 82%

“…12 Here, we show that dusp-5 KD affects the same population of cells. Based on this similarity, we investigated whether dusp-5 and snrk-1 target a common signaling pathway controlling angioblast development at the LPM.…”

Section: Dusp-5 and Snrk-1 Target A Common Signaling Pathway In Angiomentioning

confidence: 77%

“…In both the head and tail, dusp-5 ϩ angioblasts are not affected in snrk-1 mRNA-injected embryos ( Figure 3S) compared with UI embryos ( Figure 3R). Previously, 12 we showed that snrk-1 mRNA-injected embryos showed altered migration of etsrp ϩ cells to the midline. Given the current study, these results suggest that dusp-5 ϩ etsrp ϩ angioblasts exist in the In high-power images of snrk-1 mRNA-injected embryos (Y), the patterning of dusp-5 ؉ cells is affected compared with similar regions in WT embryos (X), and they also appear closer to the midline in snrk-1 mRNA-injected embryos with more diffuse distribution.…”

Section: Snrk-1 Overexpression Alters Migration Of Dusp-5 ؉ Angioblasmentioning

confidence: 80%

“…Our findings that snrk-1 KD causes migration defects in HUVECs and in etsrp ϩ angioblasts in ZF further bolster this assumption. 12 We initiated the current study to investigate whether dusp-5, a candidate gene identified in 2 independent microarray studies 10,11 shows vascular specific function. We obtained similar results of altered etsrp ϩ cells along the LPM in dusp-5 LOF embryos as seen previously for snrk-1 LOF, 12 suggesting that dusp-5 and snrk-1 may function together during embryonic vascular development.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we had identified in a gain-of-function (GOF) and LOF study for a serine-threonine kinase member of the sucrose nonfermenting kinase family, Snrk-1, that it increased or decreased, respectively, the same etsrp ϩ angioblast population at the LPM. 12 Taking these findings together, we hypothesized that, during vascular development, Dusp-5 and Snrk-1 function together in controlling angioblast numbers at the LPM. In this study, we show that dusp-5 is expressed in angioblasts in the embryonic ZF and is essential for vascular development in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Dusp-5 and Snrk-1 coordinately function during vascular development and disease

Pramanik

Chun

Garnaas

et al. 2009

Blood

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IntroductionThe mitogen-activated protein kinase (MAPK) pathway 1 represent a key signal integration step inside the cell for various extracellular stimuli. 2 At least 4 MAPK families have been identified: the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38, and Erk5. Each MAPK is activated by specific MAPK kinases (Mkks or Meks), which in turn are regulated by Mek kinases (Mekks). To date, several members of the MAPK family, including Erk5 3 and Mekk3, 4 have been implicated in vascular development in vivo. 5 Furthermore, MAPKs are often associated with pathologic responses, such as stress, apoptosis, inflammation, and cell proliferation. 5,6 In terms of vascular conditions, differential expression of active MAPKs was noticed in several types of hemangiomas, 7 the most common vascular tumor of infancy and childhood, 8 and the presence of immunoreactive phosphorylated MAPK inversely correlate with degree of malignancy. 7 Therefore, from a drug discovery standpoint, vascular specific components of MAPKs cascade are promising drug targets. 6 MAPKs are activated by dual phosphorylation of tyrosine and threonine residues in their activation loops. To control MAPK activation, a family of proteins called dual-specificity protein tyrosine phosphatases (DUSPs) dephosphorylate both residues. 9 DUSPs come in 2 varieties: dual-specificity MAPK phosphatases and atypical DUSPs. A dual specific phosphatase, Dusp-5, was recently identified by 2 independent microarray studies as a vascular-specific gene, 10,11 and we hypothesized that dusp-5 plays a specific role in vascular development. To investigate dusp-5 function, we initiated a loss-of-function (LOF) study in zebrafish (ZF). We identified that dusp-5 LOF embryos showed enhanced etsrp ϩ angioblasts at the lateral plate mesoderm (LPM). Recently, we had identified in a gain-of-function (GOF) and LOF study for a serine-threonine kinase member of the sucrose nonfermenting kinase family, Snrk-1, that it increased or decreased, respectively, the same etsrp ϩ angioblast population at the LPM. 12 Taking these findings together, we hypothesized that, during vascular development, Dusp-5 and Snrk-1 function together in controlling angioblast numbers at the LPM. In this study, we show that dusp-5 is expressed in angioblasts in the embryonic ZF and is essential for vascular development in vivo. We show that loss of Dusp-5 function in vitro causes apoptosis of endothelial cells (ECs), and Dusp-5 and Snrk-1 target a common signaling pathway responsible for maintaining angioblast populations along the LPM. Snrk-1 ectopically induces etsrp ϩ angioblasts in the LPM, which is blocked by Dusp-5 that functions downstream of Snrk-1. In addition, we have identified mutations in dusp-5 and snrk-1 in the lesional tissue of many vascular anomaly patient samples, suggesting a critical role for this pathway in disease. Methods ZF stocksWild-type ZF (TuAB strain) were grown and maintained at 28.5°C. 13 All procedures were performed according to animal protoc...

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Section: Ectopic Induction Of Etsrp ؉ Angioblasts By Snrk-1 Is Blockesupporting

confidence: 82%

Section: Dusp-5 and Snrk-1 Target A Common Signaling Pathway In Angiomentioning

confidence: 77%

Section: Snrk-1 Overexpression Alters Migration Of Dusp-5 ؉ Angioblasmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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