The novel protein kinase Vlk is essential for stromal function of mesenchymal cells

Kinoshita, Masaki; Era, Takumi; Jakt, Lars Martin; Nishikawa, Shin Ichi

doi:10.1242/dev.026435

Cited by 45 publications

(106 citation statements)

References 34 publications

(37 reference statements)

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“…During embryonic development, as limbs become evident around E9.5, Adtk1 transcripts could always be detected in these structures; curiously during later stages, Adtk1 expression in the limbs is restricted to the most proximal part of the limb (data not shown). This set of data corroborates the data recently published both by Imuta et al, 2009 andKinoshita et al, 2009 describing Adtk1 null mutants (Pkdcc and Vlk) although the phenotypes are a little milder probably due to background differences. Consequently, the analysis of these null mutants was not scrutinized further.…”

Section: Fig 8 (Left) Schematic Representation Of Targeted Deletionsupporting

confidence: 91%

“…However, Adtk1 targeted inactivation resulted in shorter limbs and no anterior structure defects as we expected. This phenotype is not as severe as the one reported by Imuta et al, 2009 andKinoshita et al, 2009, which besides shorter limbs, also report cleft palate defects, which were not found in our analysis of Adtk1 mutants. This phenotypical difference could be accounted for, by the fact both Imuta el al.…”

Section: Discussionsupporting

confidence: 55%

“…This phenotypical difference could be accounted for, by the fact both Imuta el al. 2009 andKinoshita et al, 2009 used TT2 ES cells, whereas the targeting here reported was performed in C57Bl/6-cBrd mixed background. It is known that differences in genetic background, which are characterized by specific single nucleotide polymorphisms (SNPs), can be associated with regulatory variations, affecting gene expression levels, and giving rise to different phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…Also, it has a proline-rich region between aminoacids 75 and 128, and an arginine-rich region between aminoacids 49 and 106 (Imuta et al, 2009;Kinoshita et al, 2009). MAd1 was renamed Adtk1 which stands for Anterior Distal Tyrosine Kinase 1.…”

Section: Selection Of Novel Genes Upregulated In the Avementioning

confidence: 99%

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Identification and functional analysis of novel genes expressed in the Anterior Visceral Endoderm

Gonçalves

Filipe²,

Marques³

et al. 2011

Int. J. Dev. Biol.

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During early vertebrate development, the correct establishment of the body axes is critical. The anterior pole of the mouse embryo is established when Distal Visceral Endoderm (DVE) cells migrate to form the Anterior Visceral Endoderm (AVE). Symmetrical expression of Lefty1, Cer1 and Dkk1 determines the direction of DVE migration and the future anterior side. In addition to the establishment of the Anterior-Posterior axis, the AVE has also been implicated in anterior neural specification. To better understand the role of the AVE in these processes, we have performed a differential screening using Affymetrix GeneChip technology with AVE cells isolated from cer1P-EGFP transgenic mouse embryos. We found 175 genes which were upregulated in the AVE and 36 genes in the Proximal-posterior sample. Using DAVID software, we characterized the AVE cell population regarding cellular component, molecular function and biological processes. Among the genes that were found to be upregulated in the AVE, several novel genes were identified. Four of these transcripts displaying high-fold change in the AVE were further characterized by in situ hybridization in early stages of development in order to validate the screening. From those four selected genes, one, denominated Adtk1, was chosen to be functionally characterized by targeted inactivation in ES cells. Adtk1 encodes for a serine/threonine kinase. Adtk1 null mutants are smaller and present short limbs due to decreased mineralization, suggesting a potential role in chondrogenesis during limb development. Taken together, these data point to the importance of reporting novel genes present in the AVE.

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Section: Fig 8 (Left) Schematic Representation Of Targeted Deletionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Selection Of Novel Genes Upregulated In the Avementioning

confidence: 99%

See 2 more Smart Citations

Identification and functional analysis of novel genes expressed in the Anterior Visceral Endoderm

Gonçalves

Filipe²,

Marques³

et al. 2011

Int. J. Dev. Biol.

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“…Another newly identified kinase: vertebrate lonesome kinase (VLK)-which shows preference for Tyr residues-also localizes in the secretory pathway (9,10). High expression level of VLK was detected in platelets, and upon stimulation by the thrombin receptor activating peptide (TRAP) VLK was rapidly and quantitatively released from platelets.…”

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confidence: 99%

Extracellular Protein Phosphorylation, the Neglected Side of the Modification

Klement

Medzihradszky

2017

Molecular & Cellular Proteomics

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The very existence of extracellular phosphorylation has been questioned for a long time, although casein phosphorylation was discovered a century ago. In addition, several modification sites localized on secreted proteins or on extracellular or lumenal domains of transmembrane proteins have been catalogued in large scale phosphorylation analyses, though in most such studies this aspect of cellular localization was not considered. Our review presents examples when additional analyses were performed on already public data sets that revealed a wealth of information about this "neglected side" of the modification. We also sum up accumulated knowledge about extracellular phosphorylation, including the discovery of Golgi-residing kinases and the special difficulties encountered in targeted analyses. We hope future phosphorylation studies will not ignore the existence of phosphorylation outside of the cell, and further discoveries will shed more light on its biological role. Molecular & Cellular Proteomics 16: 10.1074/mcp.O116.064188, 1-7, 2017.

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A morpholino‐based screen to identify novel genes involved in craniofacial morphogenesis

Melvin

Feng

Hernandez-Lagunas

et al. 2013

Developmental Dynamics

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BACKGROUND The regulatory mechanisms underpinning facial development are conserved between diverse species. Therefore, results from model systems provide insight into the genetic causes of human craniofacial defects. Previously, we generated a comprehensive dataset examining gene expression during development and fusion of the mouse facial prominences. Here, we used this resource to identify genes that have dynamic expression patterns in the facial prominences, but for which only limited information exists concerning developmental function. RESULTS This set of ~80 genes was used for a high throughput functional analysis in the zebrafish system using Morpholino gene knockdown technology. This screen revealed three classes of cranial cartilage phenotypes depending upon whether knockdown of the gene affected the neurocranium, viscerocranium, or both. The targeted genes that produced consistent phenotypes encoded proteins linked to transcription (meis1, meis2a, tshz2, vgll4l), signaling (pkdcc, vlk, macc1, wu:fb16h09), and extracellular matrix function (smoc2). The majority of these phenotypes were not altered by reduction of p53 levels, demonstrating that both p53 dependent and independent mechanisms were involved in the craniofacial abnormalities. CONCLUSIONS This Morpholino-based screen highlights new genes involved in development of the zebrafish craniofacial skeleton with wider relevance to formation of the face in other species, particularly mouse and human.

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The novel protein kinase Vlk is essential for stromal function of mesenchymal cells

Cited by 45 publications

References 34 publications

Identification and functional analysis of novel genes expressed in the Anterior Visceral Endoderm

Identification and functional analysis of novel genes expressed in the Anterior Visceral Endoderm

Extracellular Protein Phosphorylation, the Neglected Side of the Modification

A morpholino‐based screen to identify novel genes involved in craniofacial morphogenesis

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