Genes regulated by potassium channel tetramerization domain containing 15 (Kctd15) in the developing neural crest

Wong, Thomas Chi Bun; Rebbert, Martha L.; Wang, Chengdong; Chen, Xiongfong; Heffer, Alison; Zarelli, Valeria E.P.; Dawid, Igor B.; Zhao, Hui

doi:10.1387/ijdb.160058id

Cited by 19 publications

(22 citation statements)

References 64 publications

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“…Further, we analyzed kctd15a and kctd15b transcript levels in our double mutants. Kctd15 has previously been reported to repress its own transcription [ 24 ]. Both kctd15a and kctd15b transcript levels are significantly up-regulated at several developmental time points in kctd15 mutants ( S1D Fig ).…”

Section: Resultsmentioning

confidence: 99%

Generation and characterization of Kctd15 mutations in zebrafish

et al. 2017

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Potassium channel tetramerization domain containing 15 (Kctd15) was previously found to have a role in early neural crest (NC) patterning, specifically delimiting the region where NC markers are expressed via repression of transcription factor AP-2a and inhibition of Wnt signaling. We used transcription activator-like effector nucleases (TALENs) to generate null mutations in zebrafish kctd15a and kctd15b paralogs to study the in vivo role of Kctd15. We found that while deletions producing frame-shift mutations in each paralog showed no apparent phenotype, kctd15a/b double mutant zebrafish are smaller in size and show several phenotypes including some affecting the NC, such as expansion of the early NC domain, increased pigmentation, and craniofacial defects. Both melanophore and xanthophore pigment cell numbers and early markers are up-regulated in the double mutants. While we find no embryonic craniofacial defects, adult mutants have a deformed maxillary segment and missing barbels. By confocal imaging of mutant larval brains we found that the torus lateralis (TLa), a region implicated in gustatory networks in other fish, is absent. Ablation of this brain tissue in wild type larvae mimics some aspects of the mutant growth phenotype. Thus kctd15 mutants show deficits in the development of both neural crest derivatives, and specific regions within the central nervous system, leading to a strong reduction in normal growth rates.

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Section: Resultsmentioning

confidence: 99%

Generation and characterization of Kctd15 mutations in zebrafish

et al. 2017

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“…In agreement with a role for Kctd15 paralogs inhibiting Tfap2a in the NC, overexpression of kctd15a or kctd15b mRNA in zebrafish resulted in a phenotype very similar to that of tfap2a/c double mutants, signifying a loss of NC [70]. Similarly, injection of kctd15 mRNA decreased expression levels of NC markers foxd3, sox9, sox10, and tfap2e in Xenopus animal cap explants induced to express NC genes [199]. In contrast, zebrafish injected with morpholinos against kctd15a/b displayed expansion of NC markers, as well as a phenotype of small heads, abnormal somites, and increased pigmentation [70].…”

Section: Introductionsupporting

confidence: 65%

Transcription factor AP2 paralogs in melanocytes and melanoma

Seberg¹

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There are many people who have contributed to this thesis, and I greatly appreciate everything they have done for me during my graduate training. First, I would like to thank my research mentor Dr. Robert Cornell, who has provided excellent guidance in this project and so many opportunities to develop my skills as a scientist. He has always encouraged a collaborative atmosphere and open discussion of ideas, and I know that everything I have learned from him will benefit me greatly in my future career. Second, I would like to thank my thesis committee for their advice on this project, as well as the various other members of Genetics program and the ACB department who have lent their advice and technical expertise. I am also very grateful to the numerous collaborators who have generously contributed data to this project, particularly Stacie Loftus and Bill Pavan at NHGRI, and Eric Van Otterloo and Trevor Williams at UC-Denver. Third, I would like to thank everyone I have gotten to work with in the Cornell lab: Greg Bonde for his help with everything fish-related and many other experiments too, Huan Liu for his help with bioinformatic analysis, my undergraduate assistant Mikaela Mallin for her diligence working on the KCTD15 project over the last 3 years, and all of the other graduate students and undergrads who have made working in the lab so much fun. Finally, I would like to thank my family for being my constant source of encouragement and always listening to me talk about science. I am truly fortunate to have so many supportive people in my life.

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“… 12 Current data show that ZSWIM5 expression is high in normal brain and malignant gliomas. 13 – 15 Besides this, we have acquired limited knowledge on the function of ZSWIM5.…”

Section: Discussionmentioning

confidence: 99%

“…ZSWIM5 was predicted to localize to the nucleus and interact with DNA or other proteins in different contexts. 13 – 15 However, we have limited information regarding the expression and functions of ZSWIM5, especially in malignant tumors.…”

Section: Introductionmentioning

confidence: 99%

A novel SWIM domain protein ZSWIM5 inhibits the malignant progression of non-small-cell lung cancer

Liu

et al. 2018

CMAR

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PurposeZinc finger SWIM-type containing 5 (ZSWIM5) is a newly discovered protein, which contains a novel zinc-chelating domain SWIM (CxCxnCxH), and is predicted to interact with DNA or proteins. Currently, the knowledge of functions of ZSWIM5 remains limited. In this study, we aimed to elucidate the biological functions of ZSWIM5 and their mechanisms.Patients and methodsWe detected the expression of ZSWIM5 in samples from 139 cases of non-small-cell lung cancer (NSCLC) patients and six cell lines using immunohistochemistry and Western blot. Moreover, we explored the biological functions of ZSWIM5 in lung cancer cells by siRNA interference and cDNA transfection of ZSWIM5.ResultsThe results showed that compared with adjacent non-tumor lung tissues, ZSWIM5 expression was significantly decreased in NSCLC tissues (P=0.0199) and that the ZSWIM5-positive rate in non-tumor tissues (76.67%) was notably higher than that in NSCLC tissues (40.29%). ZSWIM5 expression in human normal bronchial epithelial cells was also much higher than that in lung cancer lines (P<0.001). ZSWIM5-negative expression was significantly related to TNM stage (P<0.001), lymph node metastasis (P=0.002), and poor prognosis (P<0.001) of NSCLC patients. MTT and colony formation assays showed that ZSWIM5 could inhibit the proliferation and colony formation abilities of lung cancer cells. Meanwhile, the results of transwell and wound healing assays showed that ZSWIM5 could suppress the invasion and migration of lung cancer cells. Further investigation revealed that ZSWIM5 could downregulate cyclin D1, cyclin E, cyclin A2, MMP2, and MMP9 expression, which affected the proliferation, invasion, and migration abilities of lung cancer cells.ConclusionZSWIM5 could inhibit the malignant progression of NSCLC by affecting the expression of cyclins and MMPs.

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Genes regulated by potassium channel tetramerization domain containing 15 (Kctd15) in the developing neural crest

Cited by 19 publications

References 64 publications

Generation and characterization of Kctd15 mutations in zebrafish

Generation and characterization of Kctd15 mutations in zebrafish

Transcription factor AP2 paralogs in melanocytes and melanoma

A novel SWIM domain protein ZSWIM5 inhibits the malignant progression of non-small-cell lung cancer

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