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Sall4 isoforms act during proximal–distal and anterior–posterior axis formation in the mouse embryo
Author(s) -
Uez Nikolas,
Lickert Heiko,
Kohlhase Jürgen,
de Angelis Martin Hrabe,
Kühn Ralf,
Wurst Wolfgang,
Floss Thomas
Publication year - 2008
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20421
Subject(s) - gastrulation , epiblast , biology , embryonic stem cell , ectoderm , wnt signaling pathway , endoderm , embryogenesis , mutant , microbiology and biotechnology , phenotype , primitive streak , embryo , genetics , anatomy , gene , signal transduction
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/β‐catenin signaling to elongate the AP axis during gastrulation. This observation was supported through genetic interaction with β‐ catenin mutants, since compound heterozygous mutants recapitulated the defects of Wnt3a mutants in posterior development. genesis 46:463–477, 2008. © 2008 Wiley‐Liss, Inc.