The role of the proline-rich domain of Ssdp1 in the modular architecture of the vertebrate head organizer.
Lim1, Ssdp1, and Ldb1 proteins are components of the Ldb1-associated transcriptional complex, which is important in the head-organizing activity during early mouse development. Depletion of each individual protein alone causes a headless phenotype. To explore in more detail the modular architecture of the complex, we have generated two different gene-trapped mouse lines that express truncated forms of Ssdp1. Embryos derived from the gene-trapped line that encodes a truncated Ssdp1 lacking the proline-rich sequence exhibit a lethal abnormal head-development phenotype, resembling mouse embryos deficient for Lim1, Ssdp1, or Otx2 genes. Embryos derived from the second gene-trapped line, in which most of the proline-rich domain of Ssdp1 is retained, did not show abnormalities in head development. Our data demonstrate that components of the Ldb1-dependent module can be subdivided further into discrete functional domains and that the proline-rich stretch of Ssdp1 is critical for embryonic head development. Furthermore, phylogenetic comparisons revealed that in Caenorhabditis elegans, a similar proline-rich sequence is absent in Ssdp but present in Ldb1. We conclude that although the overall architecture of the Ldb1-dependent module has been preserved, the genetic specification of its individual components has diversified during evolution, without compromising the function of the module.
Enkhmandakh
Badam
B
Department of Molecular, Cellular, and Craniofacial Biology, Birth Defects Center, University of Louisville, Louisville, KY 40292, USA.
Makeyev
Alexandr V
AV
Bayarsaihan
Dashzeveg
D
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology*; D004625:Embryo, Nonmammalian; D006257:Head / Q000033:anatomy & histology / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D020897:Organizers, Embryonic; D011392:Proline / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014157:Transcription Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; C102084:Ldb1 protein, mouse; C499523:Lhx1 protein, mouse; D046911:Macromolecular Substances; C504093:Ssbp3 protein, mouse; D014157:Transcription Factors; D011392:Proline