Ssdp1 regulates head morphogenesis of mouse embryos by activating the Lim1-Ldb1 complex.
The transcriptional activity of LIM-homeodomain (LIM-HD) proteins is regulated by their interactions with various factors that bind to the LIM domain. We show that reduced expression of single-stranded DNA-binding protein 1 (Ssdp1), which encodes a co-factor of LIM domain interacting protein 1 (Ldb1), in the mouse mutant headshrinker (hsk) disrupts anterior head development by partially mimicking Lim1 mutants. Although the anterior visceral endoderm and the anterior definitive endoderm, which together comprise the head organizer, were able to form normally in Ssdp1(hsk/hsk) mutants, development of the prechordal plate was compromised. Head development is partially initiated in Ssdp1(hsk/hsk) mutants, but neuroectoderm tissue anterior to the midbrain-hindbrain boundary is lost, without a concomitant increase in apoptosis. Cell proliferation is globally reduced in Ssdp1(hsk/hsk) mutants, and approximately half also exhibit smaller body size, similar to the phenotype observed in Lim1 and Ldb1 mutants. We also show that Ssdp1 contains an activation domain and is able to enhance transcriptional activation through a Lim1-Ldb1 complex in transfected cells, and that Ssdp1 interacts genetically with Lim1 and Ldb1 in both head development and body growth. These results suggest that Ssdp1 regulates the development of late head organizer tissues and body growth by functioning as an essential activator component of a Lim1 complex through interaction with Ldb1.
Nishioka
Noriyuki
N
Laboratory for Embryonic Induction, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Nagano
Seiichi
S
Nakayama
Rika
R
Kiyonari
Hiroshi
H
Ijiri
Takashi
T
Taniguchi
Kenichiro
K
Shawlot
William
W
Hayashizaki
Yoshihide
Y
Westphal
Heiner
H
Behringer
Richard R
RR
Matsuda
Yoichi
Y
Sakoda
Saburo
S
Kondoh
Hisato
H
Sasaki
Hiroshi
H
D000818:Animals; D015152:Blotting, Northern; D049109:Cell Proliferation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006257:Head / Q000196:embryology*; D018398:Homeodomain Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D020287:In Situ Nick-End Labeling; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; D051379:Mice / Q000196:embryology*; D008822:Mice, Transgenic; D009024:Morphogenesis; D046912:Multiprotein Complexes / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D019076:Transgenes / Q000235:genetics
D017931:DNA Primers; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; C102084:Ldb1 protein, mouse; C499523:Lhx1 protein, mouse; D046912:Multiprotein Complexes; C504092:Ssbp2 protein, mouse; C504093:Ssbp3 protein, mouse; D014157:Transcription Factors