Role of delta-like-4/Notch in the formation and wiring of the lymphatic network in zebrafish.
OBJECTIVE
To study whether Notch signaling, which regulates cell fate decisions and vessel morphogenesis, controls lymphatic development.


RESULTS
In zebrafish embryos, sprouts from the axial vein have lymphangiogenic potential because they give rise to the first lymphatics. Knockdown of delta-like-4 (Dll4) or its receptors Notch-1b or Notch-6 in zebrafish impaired lymphangiogenesis. Dll4/Notch silencing reduced the number of sprouts producing the string of parchordal lymphangioblasts; instead, sprouts connecting to the intersomitic vessels were formed. At a later phase, Notch silencing impaired navigation of lymphatic intersomitic vessels along their arterial templates.


CONCLUSIONS
These studies imply critical roles for Notch signaling in the formation and wiring of the lymphatic network.
Geudens
Ilse
I
Vesalius Research Center, VIB, Leuven, Belgium.
Herpers
Robert
R
Hermans
Karlien
K
Segura
Inmaculada
I
Ruiz de Almodovar
Carmen
C
Bussmann
Jeroen
J
De Smet
Frederik
F
Vandevelde
Wouter
W
Hogan
Benjamin M
BM
Siekmann
Arndt
A
Claes
Filip
F
Moore
John C
JC
Pistocchi
Anna Silvia
AS
Loges
Sonja
S
Mazzone
Massimiliano
M
Mariggi
Giovanni
G
Bruyère
Françoise
F
Cotelli
Franco
F
Kerjaschki
Dontscho
D
Noël
Agnes
A
Foidart
Jean-Michel
JM
Gerhardt
Holger
H
Ny
Annelii
A
Langenberg
Tobias
T
Lawson
Nathan D
ND
Duckers
Henricus J
HJ
Schulte-Merker
Stefan
S
Carmeliet
Peter
P
Dewerchin
Mieke
M
D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000378:metabolism; D019556:COS Cells; D002465:Cell Movement; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D004625:Embryo, Nonmammalian / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D042583:Lymphangiogenesis / Q000235:genetics; D008208:Lymphatic System / Q000196:embryology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013897:Thoracic Duct / Q000196:embryology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C064045:delta protein
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