Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Smads 1, 5, and 8 are the intracellular mediators for the bone morphogenetic proteins (BMPs), which play crucial roles during mammalian development. Previous research has shown that Smad1 is important in the formation of the allantois, while Smad5 has been shown to be critical in the process of angiogenesis. To further analyze the BMP-responsive Smads, we disrupted the murine Smad8 gene utilizing the Cre/loxP system. A Smad8 hypomorphic allele (Smad8(Deltaexon3)) was constructed that contains an in-frame deletion of exon 3, removing one-third of the MH2 domain and a small portion of the linker region. Xenopus injection assays indicated that this Smad8 deletion allele is still functional but has reduced ventralizing capability compared to the wild type. Although Smad8(Deltaexon3/Deltaexon3) embryos are phenotypically normal, homozygotes of another hypomorphic allele of Smad8 (Smad8(3loxP)) containing a neomycin cassette within intron 3, phenocopy an embryonic brain defect observed in roughly 22% of Smad1(+/)(-) embryos analyzed at embryonic day 11.5. These observations suggest that BMP-responsive Smads have critical functions in the development of the mammalian central nervous system.
Anderson,
Chordin and noggin promote organizing centers of forebrain development in the mouse.
2002, Pubmed
Anderson,
Chordin and noggin promote organizing centers of forebrain development in the mouse.
2002,
Pubmed
Ang,
HNF-3 beta is essential for node and notochord formation in mouse development.
1994,
Pubmed
Attisano,
The Smads.
2001,
Pubmed
Attisano,
Signal transduction by the TGF-beta superfamily.
2002,
Pubmed
Bachiller,
The organizer factors Chordin and Noggin are required for mouse forebrain development.
2000,
Pubmed
Chang,
Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects.
1999,
Pubmed
Chang,
Smad5 is essential for left-right asymmetry in mice.
2000,
Pubmed
Deng,
Fibroblast growth factor receptor 3 is a negative regulator of bone growth.
1996,
Pubmed
Deng,
Murine FGFR-1 is required for early postimplantation growth and axial organization.
1994,
Pubmed
,
Xenbase
Dick,
Expression of Smad1 and Smad2 during embryogenesis suggests a role in organ development.
1998,
Pubmed
Dickinson,
Dorsalization of the neural tube by the non-neural ectoderm.
1995,
Pubmed
Dodd,
Spatial regulation of axonal glycoprotein expression on subsets of embryonic spinal neurons.
1988,
Pubmed
,
Xenbase
Ducy,
The family of bone morphogenetic proteins.
2000,
Pubmed
Dunn,
Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4.
1997,
Pubmed
,
Xenbase
Durand,
RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency.
1997,
Pubmed
Ebendal,
Bone morphogenetic proteins and their receptors: potential functions in the brain.
1998,
Pubmed
Echelard,
Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity.
1993,
Pubmed
el-Hodiri,
Interaction of the CCAAT displacement protein with shared regulatory elements required for transcription of paired histone genes.
1995,
Pubmed
,
Xenbase
Epstein,
Pax3 and vertebrate development.
2000,
Pubmed
Evans,
Expression of the helix-loop-helix factor Id during mouse embryonic development.
1993,
Pubmed
Furuta,
Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development.
1997,
Pubmed
Goulding,
Pax-3, a novel murine DNA binding protein expressed during early neurogenesis.
1991,
Pubmed
Henningfeld,
Smad1 and Smad4 are components of the bone morphogenetic protein-4 (BMP-4)-induced transcription complex of the Xvent-2B promoter.
2000,
Pubmed
,
Xenbase
Holzenberger,
Cre-mediated germline mosaicism: a method allowing rapid generation of several alleles of a target gene.
2000,
Pubmed
Jessell,
Neuronal specification in the spinal cord: inductive signals and transcriptional codes.
2000,
Pubmed
Kao,
The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos.
1988,
Pubmed
,
Xenbase
Lai,
Hepatocyte nuclear factor 3 alpha belongs to a gene family in mammals that is homologous to the Drosophila homeotic gene fork head.
1991,
Pubmed
Lakso,
Efficient in vivo manipulation of mouse genomic sequences at the zygote stage.
1996,
Pubmed
Lechleider,
Targeted mutagenesis of Smad1 reveals an essential role in chorioallantoic fusion.
2001,
Pubmed
Lee,
The specification of dorsal cell fates in the vertebrate central nervous system.
1999,
Pubmed
Lee,
Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord.
1998,
Pubmed
Lee,
Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification.
2000,
Pubmed
Liem,
A role for the roof plate and its resident TGFbeta-related proteins in neuronal patterning in the dorsal spinal cord.
1997,
Pubmed
,
Xenbase
Liu,
Generation of novel conditional and hypomorphic alleles of the Smad2 gene.
2004,
Pubmed
,
Xenbase
MacKenzie,
Two enhancer domains control early aspects of the complex expression pattern of Msx1.
1997,
Pubmed
Mansouri,
The role of Pax3 and Pax7 in development and cancer.
1998,
Pubmed
Mehler,
Bone morphogenetic proteins in the nervous system.
1997,
Pubmed
Meyers,
An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination.
1998,
Pubmed
Miyanaga,
A maternal Smad protein regulates early embryonic apoptosis in Xenopus laevis.
2002,
Pubmed
,
Xenbase
Nagy,
Cre recombinase: the universal reagent for genome tailoring.
2000,
Pubmed
Nakayama,
Xenopus Smad8 acts downstream of BMP-4 to modulate its activity during vertebrate embryonic patterning.
1998,
Pubmed
,
Xenbase
Nishita,
Smad8B, a Smad8 splice variant lacking the SSXS site that inhibits Smad8-mediated signalling.
1999,
Pubmed
Osoegawa,
Bacterial artificial chromosome libraries for mouse sequencing and functional analysis.
2000,
Pubmed
Pabst,
Targeted disruption of the homeobox gene Nkx2.9 reveals a role in development of the spinal accessory nerve.
2003,
Pubmed
Pera,
Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction.
2003,
Pubmed
,
Xenbase
Sasai,
Ectodermal patterning in vertebrate embryos.
1997,
Pubmed
,
Xenbase
Sater,
Evidence for antagonism of BMP-4 signals by MAP kinase during Xenopus axis determination and neural specification.
2003,
Pubmed
,
Xenbase
Sauer,
Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1.
1988,
Pubmed
Solloway,
Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup.
1999,
Pubmed
Suzuki,
Smad5 induces ventral fates in Xenopus embryo.
1997,
Pubmed
,
Xenbase
Suzuki,
Involvement of the Polycomb-group gene Ring1B in the specification of the anterior-posterior axis in mice.
2002,
Pubmed
Thomsen,
Xenopus mothers against decapentaplegic is an embryonic ventralizing agent that acts downstream of the BMP-2/4 receptor.
1996,
Pubmed
,
Xenbase
Timmer,
BMP signaling patterns the dorsal and intermediate neural tube via regulation of homeobox and helix-loop-helix transcription factors.
2002,
Pubmed
Trainor,
Patterning the cranial neural crest: hindbrain segmentation and Hox gene plasticity.
2000,
Pubmed
Tremblay,
Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation.
2001,
Pubmed
,
Xenbase
Walther,
Pax-6, a murine paired box gene, is expressed in the developing CNS.
1991,
Pubmed
Warren,
Roles of Pax-6 in murine diencephalic development.
1997,
Pubmed
Wilkinson,
Molecular approaches to the segmentation of the hindbrain.
1990,
Pubmed
Winnier,
Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse.
1995,
Pubmed
Wozney,
Novel regulators of bone formation: molecular clones and activities.
1988,
Pubmed
Wrana,
The Smad pathway.
2000,
Pubmed
Wrana,
Crossing Smads.
2000,
Pubmed
Xu,
Direct removal in the mouse of a floxed neo gene from a three-loxP conditional knockout allele by two novel approaches.
2001,
Pubmed
Yang,
Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5.
1999,
Pubmed
Zhao,
Consequences of knocking out BMP signaling in the mouse.
2003,
Pubmed
