Sall1, sall2, and sall4 are required for neural tube closure in mice.
Four homologs to the Drosophila homeotic gene spalt (sal) exist in both humans and mice (SALL1 to SALL4/Sall1 to Sall4, respectively). Mutations in both SALL1 and SALL4 result in the autosomal-dominant developmental disorders Townes-Brocks and Okihiro syndrome, respectively. In contrast, no human diseases have been associated with SALL2 to date, and Sall2-deficient mice have shown no apparent abnormal phenotype. We generated mice deficient in Sall2 and, contrary to previous reports, 11% of our Sall2-deficient mice showed background-specific neural tube defects, suggesting that Sall2 has a role in neurogenesis. To investigate whether Sall4 may compensate for the absence of Sall2, we generated compound Sall2 knockout/Sall4 genetrap mutant mice. In these mutants, the incidence of neural tube defects was significantly increased. Furthermore, we found a similar phenotype in compound Sall1/4 mutant mice, and in vitro studies showed that SALL1, SALL2, and SALL4 all co-localized in the nucleus. We therefore suggest a fundamental and redundant function of the Sall proteins in murine neurulation, with the heterozygous loss of a particular SALL protein also possibly compensated in humans during development.
Böhm
Johann
J
Institut für Humangenetik und Anthropologie, Universität Freiburg, Freiburg, Germany.
Buck
Anja
A
Borozdin
Wiktor
W
Mannan
Ashraf U
AU
Matysiak-Scholze
Uta
U
Adham
Ibrahim
I
Schulz-Schaeffer
Walter
W
Floss
Thomas
T
Wurst
Wolfgang
W
Kohlhase
Jürgen
J
Barrionuevo
Francisco
F
D000818:Animals; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D009432:Neural Crest / Q000378:metabolism / Q000473:pathology; D054259:Neural Tube / Q000196:embryology* / Q000378:metabolism*; D009436:Neural Tube Defects / Q000378:metabolism / Q000473:pathology; D054261:Neurulation; D012886:Skull / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C491254:Sall1 protein, mouse; C403266:Sall2 protein, mouse; C509167:Sall4 protein, mouse; D014157:Transcription Factors