Cell lineage of timed cohorts ofTbx6-expressing cells in wild type andTbx6mutant embryos

Abstract

Tbx6 is a T-box transcription factor with multiple roles in embryonic development as evidenced by dramatic effects on mesoderm cell fate determination, left/right axis determination, and somite segmentation in mutant mice. The expression of Tbx6 is restricted to the primitive streak and presomitic mesoderm, but some of the phenotypic features of mutants are not easily explained by this expression pattern. We have used genetically-inducible fate mapping to trace the fate of Tbx6-expressing cells in wild-type and mutant embryos to explain some of the puzzling features of the mutant phenotype. We created an inducible Tbx6-creERT2 transgenic mouse in which cre expression closely recapitulates endogenous Tbx6 expression both temporally and spatially. Using a lacZ-based Cre reporter and timed tamoxifen injections, we followed temporally overlapping cohorts of cells that had expressed Tbx6 and found contributions to virtually all mesodermally-derived embryonic structures as well as the extraembryonic allantois. Contribution to the endothelium of major blood vessels may account for the embryonic death of homozygous mutant embryos. In mutant embryos, Tbx6-creERT2-traced cells contributed to the abnormally segmented anterior somites and formed the characteristic ectopic neural tubes. Retention of cells in the mutant tail bud indicates a deficiency in migratory behavior of the mutant cells and the presence of Tbx6-creERT2-traced cells in the notochord, a node derivative provides a possible explanation for the heterotaxia seen in mutant embryos.

Co-expression of Tbx6 and Sox2 identifies a novel transient neuromesoderm progenitor cell state

“…Our analysis also revealed a contribution of Tbx6 reporter-positive cells to a number of tissues including posterior neural crest (Fig. S4) (Concepcion et al, 2017).…”

Impaired intermediate formation in mouse embryos expressing reduced levels of Tbx6

“…This is a rare event in the Tbx6 rv/rv embryos that usually form at least one kidney. Abbreviations: pn, pronephros; ub, ureteric bud; g, gonad line to lineage trace cells that expressed Tbx6 revealing that timedinduction starting at e7.5-e8.5 resulted in labeled cells in the mesonephric tubules and metanephric primordia (Concepcion et al, 2017). This is perhaps not surprising since this would label cells in the PS, which are known to express Tbx6 (Chapman, Agulnik, Hancock, Silver, & Papaioannou, 1996).…”

“…In the chick, lineage‐tracing studies showed that PAM contributes to the renal stromal cells of the meso‐ and metanephros (Guillaume et al, ). More recent studies used a Tbx6‐Cre‐ERT2 line to lineage trace cells that expressed Tbx6 revealing that timed‐induction starting at e7.5–e8.5 resulted in labeled cells in the mesonephric tubules and metanephric primordia (Concepcion et al, ). This is perhaps not surprising since this would label cells in the PS, which are known to express Tbx6 (Chapman, Agulnik, Hancock, Silver, & Papaioannou, ).…”

Tbx6controls left-right asymmetry through regulation ofGdf1

“…This study focuses on the T-box gene Tbx6 that is expressed between embryonic day (E) 6.5 and E13.5 in the primitive streak, the presomitic mesoderm and the tail bud, but not in the node, although node precursors do express the gene ( Concepcion et al, 2017 ). Tbx6 null mutants die around E9.5 with defects in anterior somite patterning, ectopic neural tubes and an enlarged tail bud ( Chapman et al, 1996 ; Chapman and Papaioannou, 1998 ; Takemoto et al, 2011 ).…”