title: Sall4 isoforms act during proximal-distal and anterior-posterior axis formation in the mouse embryo.
abstract: Reciprocal signals from embryonic and extra-embryonic tissues pattern the embryo in proximal-distal (PD) and anterior-posterior (AP) fashion. Here we have analyzed three gene trap mutations of Sall4, of which one (Sall4-1a) led to a hypomorphic and recessive phenotype, demonstrating that Sall4-1a has yet undescribed extra-embryonic and embryonic functions in regulating PD and AP axis formation. In Sall4-1a mutants the self-maintaining autoregulatory interaction between Bmp4, Nodal and Wnt, which determines the PD axis was disrupted because of defects in the extra-embryonic visceral endoderm. More severely, two distinct Sall4 gene-trap mutants (Sall4-1a,b), resembling null mutants, failed to initiate Bmp4 expression in the extra-embryonic ectoderm and Nodal in the epiblast and were therefore unable to initiate PD axis formation. Tetraploid rescue underlined the extra-embryonic nature of the Sall4-1a phenotype and revealed a further embryonic function in Wnt/beta-catenin signaling to elongate the AP axis during gastrulation. This observation was supported through genetic interaction with beta-catenin mutants, since compound heterozygous mutants recapitulated the defects of Wnt3a mutants in posterior development.
authors.affiliation: Helmholtz Center Munich, Institute of Developmental Genetics, Ingolstaedter Landstrasse 1, Munich, Neuherberg, Germany.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Uez
authors.forename: Heiko
authors.initials: H
authors.lastname: Lickert
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kohlhase
authors.forename: Martin Hrabe
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Ralf
authors.initials: R
authors.lastname: Kühn
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Thomas
authors.initials: T
authors.lastname: Floss
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000196:embryology* / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; C509167:Sall4 protein, mouse; D014157:Transcription Factors