A Tale of Two Models: Mouse and Zebrafish as Complementary Models for Lymphatic Studies

Kim, Jun Dae; Jin, Suk Won

doi:10.14348/molcells.2014.0108

Cited by 9 publications

(13 citation statements)

References 106 publications

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“…The zebrafish is an ideal model in which to study lymphatic development (Kim and Jin, 2014). The external development and transparency of the zebrafish embryo permits direct visualization of lymphatic morphogenesis and forward genetic screens have yielded mutants affecting lymphatic development (Hogan et al, 2009a,b;Villefranc et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Vegfc acts through ERK to induce sprouting and differentiation of trunk lymphatic progenitors

et al. 2016

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There was an error published in Development 143, 3785-3795.In the Materials and Methods section we provided an incorrect serine residue number for the map2k2b mutation. The corrected section of text is as follows:An activated myc-tagged form of MEK was generated from zebrafish map2k2b by mutating serines 221 and 225 to aspartic acid (Schramek et al., 1997) by PCR, followed by BP cloning to generate pME-myc-act-map2k2b.In addition, we have since verified that the pME-myc-act-map2k2b plasmid used in the original studies and submitted to Addgene contains the correct sequence. This plasmid contains several nucleotide changes in comparison to the GenBank reference sequence (accession number: NM_001128281). However, all of these changes have been noted in a previous annotation of single nucleotide polymorphisms in the zebrafish and are naturally occurring variants (Butler et al., 2015).We apologize for any confusion that this may have caused and we thank the researchers who discovered the error for bringing it to our attention. ABSTRACTVascular endothelial growth factor C (Vegfc) activates its receptor, Flt4, to induce lymphatic development. However, the signals that act downstream of Flt4 in this context in vivo remain unclear. To understand Flt4 signaling better, we generated zebrafish bearing a deletion in the Flt4 cytoplasmic domain that eliminates tyrosines Y1226 and 1227. Embryos bearing this deletion failed to initiate sprouting or differentiation of trunk lymphatic vessels and did not form a thoracic duct. Deletion of Y1226/7 prevented ERK phosphorylation in lymphatic progenitors, and ERK inhibition blocked trunk lymphatic sprouting and differentiation. Conversely, endothelial autonomous ERK activation rescued lymphatic sprouting and differentiation in flt4 mutants. Interestingly, embryos bearing the Y1226/7 deletion formed a functional facial lymphatic network enabling them to develop normally to adulthood. By contrast, flt4 null larvae displayed hypoplastic facial lymphatics and severe lymphedema. Thus, facial lymphatic vessels appear to be the first functional lymphatic network in the zebrafish, whereas the thoracic duct is initially dispensable for lymphatic function. Moreover, distinct signaling pathways downstream of Flt4 govern lymphatic morphogenesis and differentiation in different anatomical locations.

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Section: Introductionmentioning

confidence: 99%

Vegfc acts through ERK to induce sprouting and differentiation of trunk lymphatic progenitors

et al. 2016

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“…; Blum et al . ; Kim & Jin ). In recent years, there was a growing interest in applying the principles of molecular therapy for lymphatic disorders (An & Rockson ; Nakamura & Rockson ; Shin & Rockson ).…”

Section: Introductionmentioning

confidence: 98%

“…; Aschen et al . ; Kim & Jin ) demonstrated the therapeutic benefit of increased VEGFC in a variety of small animal models of anatomical and functional deficiencies of lymphatic vessels.…”

Section: Introductionmentioning

confidence: 99%

“…The lymphatic system is indispensable for the collection and cycling of tissue-extravasated fluids, macromolecules and immune cells into the bloodstream (Guo et al 2009;Sleeman et al 2009;Tammela & Alitalo 2010;Schulte-Merker et al 2011;Marchi o et al 2013;Blum et al 2014;Kim & Jin 2014). In recent years, there was a growing interest in applying the principles of molecular therapy for lymphatic disorders (An & Rockson 2004;Nakamura & Rockson 2008;Shin & Rockson 2008).…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, there was a growing interest in applying the principles of molecular therapy for lymphatic disorders (An & Rockson 2004;Nakamura & Rockson 2008;Shin & Rockson 2008). In particular, the identification of the molecular components of lymphatic development has made it possible to generate molecular models for lymphangiogenesis (Szuba & Rockson 1998;Yoon et al 2003;An & Rockson 2004;Cheung et al 2006;Saito et al 2006;Aschen et al 2014;Kim & Jin 2014).…”

Section: Introductionmentioning

confidence: 99%

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Vascular endothelial growth factor C treatment for mouse hind limb lymphatic revascularization

Ferrão

Neto

Fonseca

et al. 2019

Veterinary Medicine & Sci

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Spontaneous lymphatic revascularization is a challenge and the establishment of new therapeutic strategies may improve life quality for patients suffering from lymphatic disorders. This study was designed to verify if VEGFC treatment improves lymphatic vascularization in a time‐dependent manner in mouse hindlimb ( HL ) after resection of the inguinal lymph node. Lymphatic vascular density (Vv) and length (Lv) were evaluated by stereology after immunohistochemistry. The control Group ( CG ) was not manipulated but received saline instead of VEGFC treatment. The surgery Group ( SG ) had the left inguinal lymph node resected but did not received VEGFC treatment. VEGFC Treated Group ( TG ) had the node resected and received VEGFC treatment. VEGFC and VEGFR 3 local expression were assessed by qPCR . There was an effect of time over Vv and Lv in the SG and significant difference between CG and SG in the regions studied (proximal, medium and distal regions) of the left HL ( LHL ). The Lv showed significant difference between CG and SG only in the medium region. The Vv and the Lv for TG were higher than the other groups. VEGFC and VEGFR 3 gene expression presented time effect in all regions of the LHL for SG and TG . Both VEGFC and VEGFR 3 gene expression presented significant difference between CG and SG , between SG and TG and between CG and TG . This study showed significant decrease in lymphatic vascularization in the left hindlimb of mice after surgical removal of the inguinal lymph node and adjacent lymphatic vessels. Exogenous VEGFC could recover lymphatic vascularization through stimulating neolymphangiogenesis.

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Toxic effects of sirolimus and everolimus on the development and behavior of zebrafish embryos

Zhang,

Qiu,

Zhou

et al. 2023

Biomedicine & Pharmacotherapy

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A Tale of Two Models: Mouse and Zebrafish as Complementary Models for Lymphatic Studies

Cited by 9 publications

References 106 publications

Vegfc acts through ERK to induce sprouting and differentiation of trunk lymphatic progenitors

Vegfc acts through ERK to induce sprouting and differentiation of trunk lymphatic progenitors

Vascular endothelial growth factor C treatment for mouse hind limb lymphatic revascularization

Toxic effects of sirolimus and everolimus on the development and behavior of zebrafish embryos

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