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Involvement of neurons and retinoic acid in lymphatic development: new insights in increased nuchal translucency

Burger, Nicole B.; Stuurman, Kyra E.; Kok, Evelien; Konijn, Tanja; Schooneman, Dennis; Niederreither, Karen; Coles, Mark; Agace, William LU ; Christoffels, Vincent M. and Mebius, Reina E., et al. (2014) In Prenatal Diagnosis 34(13). p.1312-1319
Abstract
ObjectiveIncreased nuchal translucency originates from disturbed lymphatic development. Abnormal neural crest cell (NCC) migration may be involved in lymphatic development. Because both neuronal and lymphatic development share retinoic acid (RA) as a common factor, this study investigated the involvement of NCCs and RA in specific steps in lymphatic endothelial cell (LEC) differentiation and nuchal edema, which is the morphological equivalent of increased nuchal translucency. MethodsMouse embryos in which all NCCs were fluorescently labeled (Wnt1-Cre;Rosa26(eYfp)), reporter embryos for in vivo RA activity (DR5-luciferase) and embryos with absent (Raldh2(-/-)) or in utero inhibition of RA signaling (BMS493) were investigated.... (More)
ObjectiveIncreased nuchal translucency originates from disturbed lymphatic development. Abnormal neural crest cell (NCC) migration may be involved in lymphatic development. Because both neuronal and lymphatic development share retinoic acid (RA) as a common factor, this study investigated the involvement of NCCs and RA in specific steps in lymphatic endothelial cell (LEC) differentiation and nuchal edema, which is the morphological equivalent of increased nuchal translucency. MethodsMouse embryos in which all NCCs were fluorescently labeled (Wnt1-Cre;Rosa26(eYfp)), reporter embryos for in vivo RA activity (DR5-luciferase) and embryos with absent (Raldh2(-/-)) or in utero inhibition of RA signaling (BMS493) were investigated. Immunofluorescence using markers for blood vessels, lymphatic endothelium and neurons was applied. Flow cytometry was performed to measure specific LEC populations. ResultsCranial nerves were consistently close to the jugular lymph sac (JLS), in which NCCs were identified. In the absence of RA synthesis, enlarged JLS and nuchal edema were observed. Inhibiting RA signaling in utero resulted in a significantly higher amount of precursor-LECs at the expense of mature LECs and caused nuchal edema. ConclusionsNeural crest cells are involved in lymphatic development. RA is required for differentiation into mature LECs. Blocking RA signaling in mouse embryos results in abnormal lymphatic development and nuchal edema. (c) 2014 John Wiley & Sons, Ltd. (Less)
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Prenatal Diagnosis
volume
34
issue
13
pages
1312 - 1319
publisher
John Wiley and Sons Ltd
external identifiers
  • wos:000346476200012
  • scopus:84918512306
ISSN
1097-0223
DOI
10.1002/pd.4473
language
English
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yes
id
5cf6ee31-3475-49e1-9da0-fd08bf842eb0 (old id 4944739)
date added to LUP
2015-02-03 07:06:32
date last changed
2017-09-03 03:11:38
@article{5cf6ee31-3475-49e1-9da0-fd08bf842eb0,
  abstract     = {ObjectiveIncreased nuchal translucency originates from disturbed lymphatic development. Abnormal neural crest cell (NCC) migration may be involved in lymphatic development. Because both neuronal and lymphatic development share retinoic acid (RA) as a common factor, this study investigated the involvement of NCCs and RA in specific steps in lymphatic endothelial cell (LEC) differentiation and nuchal edema, which is the morphological equivalent of increased nuchal translucency. MethodsMouse embryos in which all NCCs were fluorescently labeled (Wnt1-Cre;Rosa26(eYfp)), reporter embryos for in vivo RA activity (DR5-luciferase) and embryos with absent (Raldh2(-/-)) or in utero inhibition of RA signaling (BMS493) were investigated. Immunofluorescence using markers for blood vessels, lymphatic endothelium and neurons was applied. Flow cytometry was performed to measure specific LEC populations. ResultsCranial nerves were consistently close to the jugular lymph sac (JLS), in which NCCs were identified. In the absence of RA synthesis, enlarged JLS and nuchal edema were observed. Inhibiting RA signaling in utero resulted in a significantly higher amount of precursor-LECs at the expense of mature LECs and caused nuchal edema. ConclusionsNeural crest cells are involved in lymphatic development. RA is required for differentiation into mature LECs. Blocking RA signaling in mouse embryos results in abnormal lymphatic development and nuchal edema. (c) 2014 John Wiley & Sons, Ltd.},
  author       = {Burger, Nicole B. and Stuurman, Kyra E. and Kok, Evelien and Konijn, Tanja and Schooneman, Dennis and Niederreither, Karen and Coles, Mark and Agace, William and Christoffels, Vincent M. and Mebius, Reina E. and van de Pavert, Serge A. and Bekker, Mireille N.},
  issn         = {1097-0223},
  language     = {eng},
  number       = {13},
  pages        = {1312--1319},
  publisher    = {John Wiley and Sons Ltd},
  series       = {Prenatal Diagnosis},
  title        = {Involvement of neurons and retinoic acid in lymphatic development: new insights in increased nuchal translucency},
  url          = {http://dx.doi.org/10.1002/pd.4473},
  volume       = {34},
  year         = {2014},
}