Cdx and Hox genes differentially regulate posterior axial growth in mammalian embryos.
Hox and Cdx transcription factors regulate embryonic positional identities. Cdx mutant mice display posterior body truncations of the axial skeleton, neuraxis, and caudal urorectal structures. We show that trunk Hox genes stimulate axial extension, as they can largely rescue these Cdx mutant phenotypes. Conversely, posterior (paralog group 13) Hox genes can prematurely arrest posterior axial growth when precociously expressed. Our data suggest that the transition from trunk to tail Hox gene expression successively regulates the construction and termination of axial structures in the mouse embryo. Thus, Hox genes seem to differentially orchestrate posterior expansion of embryonic tissues during axial morphogenesis as an integral part of their function in specifying head-to-tail identity. In addition, we present evidence that Cdx and Hox transcription factors exert these effects by controlling Wnt signaling. Concomitant regulation of Cyp26a1 expression, restraining retinoic acid signaling away from the posterior growth zone, may likewise play a role in timing the trunk-tail transition.
Young
Teddy
T
Hubrecht Institute-KNAW and University Medical Center, 3584 CT Utrecht, The Netherlands.
Rowland
Jennifer Elizabeth
JE
van de Ven
Cesca
C
Bialecka
Monika
M
Novoa
Ana
A
Carapuco
Marta
M
van Nes
Johan
J
de Graaff
Wim
W
Duluc
Isabelle
I
Freund
Jean-Noël
JN
Beck
Felix
F
Mallo
Moises
M
Deschamps
Jacqueline
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D019521:Body Patterning / Q000235:genetics*; D000071616:CDX2 Transcription Factor; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism*; D005121:Extremities / Q000196:embryology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012863:Skeleton; D014157:Transcription Factors / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology; D051153:Wnt Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051153:Wnt Proteins; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase