The zebrafish van gogh mutation disrupts tbx1, which is involved in the DiGeorge deletion syndrome in humans.
The van gogh (vgo) mutant in zebrafish is characterized by defects in the ear, pharyngeal arches and associated structures such as the thymus. We show that vgo is caused by a mutation in tbx1, a member of the large family of T-box genes. tbx1 has been recently suggested to be a major contributor to the cardiovascular defects in DiGeorge deletion syndrome (DGS) in humans, a syndrome in which several neural crest derivatives are affected in the pharyngeal arches. Using cell transplantation studies, we demonstrate that vgo/tbx1 acts cell autonomously in the pharyngeal mesendoderm and influences the development of neural crest-derived cartilages secondarily. Furthermore, we provide evidence for regulatory interactions between vgo/tbx1 and edn1 and hand2, genes that are implicated in the control of pharyngeal arch development and in the etiology of DGS.
Piotrowski
Tatjana
T
National Institutes of Health, NICHD, LMG, Bldg. 6B, 9000 Rockville Pike, Bethesda, MD 20892, USA. piotrowski@neuro.utah.edu
Ahn
Dae-gwon
DG
Schilling
Thomas F
TF
Nair
Sreelaja
S
Ruvinsky
Ilya
I
Geisler
Robert
R
Rauch
Gerd-Jörg
GJ
Haffter
Pascal
P
Zon
Leonard I
LI
Zhou
Yi
Y
Foott
Helen
H
Dawid
Igor B
IB
Ho
Robert K
RK
D000595:Amino Acid Sequence; D000818:Animals; D001934:Branchial Region / Q000378:metabolism; D004062:DiGeorge Syndrome / Q000235:genetics*; D004423:Ear / Q000196:embryology; D004707:Endoderm / Q000378:metabolism; D006801:Humans; D008648:Mesoderm / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D017384:Sequence Deletion; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism*
D020825:T-Box Domain Proteins; C108625:TBX1 protein, human