First published online July 11, 2006
Development 133, 1505e (2006)
© The Company of Biologists Limited
Cooperative SALLies form organs
The human developmental Okihiro and Townes-Brocks syndromes are caused by
mutations in SALL4 and SALL1, respectively, human homologs
of the Drosophila homeotic gene spalt (sal). Both
syndromes feature limb, kidney, heart and anal deformities. Now, on
p. 3005,
Sakaki-Yumoto et al. report that the mouse homologs of sal cooperate
during anorectal, heart, brain and kidney development. To investigate the
roles of mammalian Sal-related genes in organogenesis, the researchers studied
mice carrying mutations in these genes. Unexpectedly, they discovered that
Sall4 is essential for embryonic stem cell proliferation and early
embryogenesis. Sall4 haploinsufficiency, however, causes anorectal
and heart defects; Sall4/Sall1 compound heterozygotes have
an increased incidence of these abnormalities, plus brain and kidney defects.
Consistent with this genetic interaction, the researchers found that Sall4 and
Sall1 form heterodimers. Furthermore, truncated Sall1 prevents the normal
localisation of Sall4 to heterochromatin. Because SALL1 is truncated in
Townes-Brocks patients, the authors suggest that certain abnormalities
associated with this disease might be caused by SALL1 inhibiting SALL4.
Related articles in Development:
- The murine homolog of SALL4, a causative gene in Okihiro syndrome, is essential for embryonic stem cell proliferation, and cooperates with Sall1 in anorectal, heart, brain and kidney development
- Masayo Sakaki-Yumoto, Chiyoko Kobayashi, Akira Sato, Sayoko Fujimura, Yuko Matsumoto, Minoru Takasato, Tatsuhiko Kodama, Hiroyuki Aburatani, Makoto Asashima, Nobuaki Yoshida, and Ryuichi Nishinakamura
Development 2006 133: 3005-3013.
[Abstract]
[Full Text]
