Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development.
SALL1 is a mammalian homolog of the Drosophila region-specific homeotic gene spalt (sal); heterozygous mutations in SALL1 in humans lead to Townes-Brocks syndrome. We have isolated a mouse homolog of SALL1 (Sall1) and found that mice deficient in Sall1 die in the perinatal period and that kidney agenesis or severe dysgenesis are present. Sall1 is expressed in the metanephric mesenchyme surrounding ureteric bud; homozygous deletion of Sall1 results in an incomplete ureteric bud outgrowth, a failure of tubule formation in the mesenchyme and an apoptosis of the mesenchyme. This phenotype is likely to be primarily caused by the absence of the inductive signal from the ureter, as the Sall1-deficient mesenchyme is competent with respect to epithelial differentiation. Sall1 is therefore essential for ureteric bud invasion, the initial key step for metanephros development.
Nishinakamura
R
R
Division of Stem Cell Regulation, Institute of Medical Science, The University of Tokyo, Japan. ryuichi@ims.u-tokoyo.ac.jp
Matsumoto
Y
Y
Nakao
K
K
Nakamura
K
K
Sato
A
A
Copeland
N G
NG
Gilbert
D J
DJ
Jenkins
N A
NA
Scully
S
S
Lacey
D L
DL
Katsuki
M
M
Asashima
M
M
Yokota
T
T
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000196:embryology*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014513:Ureter / Q000196:embryology*
D005819:Genetic Markers; C104146:SALL1 protein, human; C491254:Sall1 protein, mouse; D014157:Transcription Factors