TY - JOUR
T1 - Proximo-distal positional information encoded by an Fgf-regulated gradient of homeodomain transcription factors in the vertebrate limb
AU - Delgado, Irene
AU - López-Delgado, Alejandra C.
AU - Roselló Díez, Alberto
AU - Giovinazzo, Giovanna
AU - Cadenas, Vanessa
AU - Fernández-De-Manuel, Laura
AU - Sánchez-Cabo, Fátima
AU - Anderson, Matthew J.
AU - Lewandoski, Mark
AU - Torres, Miguel
N1 - Publisher Copyright:
© 2020 The Authors.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/6
Y1 - 2020/6
N2 - The positional information theory proposes that a coordinate system provides information to embryonic cells about their position and orientation along a patterning axis. Cells interpret this information to produce the appropriate pattern. During development, morphogens and interpreter transcription factors provide this information. We report a gradient of Meis homeodomain transcription factors along the mouse limb bud proximo-distal (PD) axis antiparallel to and shaped by the inhibitory action of distal fibroblast growth factor (FGF). Elimination of Meis results in premature limb distalization and HoxA expression, proximalization of PD segmental borders, and phocomelia. Our results show that Meis transcription factors interpret FGF signaling to convey positional information along the limb bud PD axis. These findings establish a new model for the generation of PD identities in the vertebrate limb and provide a molecular basis for the interpretation of FGF signal gradients during axial patterning.
AB - The positional information theory proposes that a coordinate system provides information to embryonic cells about their position and orientation along a patterning axis. Cells interpret this information to produce the appropriate pattern. During development, morphogens and interpreter transcription factors provide this information. We report a gradient of Meis homeodomain transcription factors along the mouse limb bud proximo-distal (PD) axis antiparallel to and shaped by the inhibitory action of distal fibroblast growth factor (FGF). Elimination of Meis results in premature limb distalization and HoxA expression, proximalization of PD segmental borders, and phocomelia. Our results show that Meis transcription factors interpret FGF signaling to convey positional information along the limb bud PD axis. These findings establish a new model for the generation of PD identities in the vertebrate limb and provide a molecular basis for the interpretation of FGF signal gradients during axial patterning.
KW - Meis
KW - limb development
KW - Proximo-distal
UR - http://www.scopus.com/inward/record.url?scp=85086626320&partnerID=8YFLogxK
U2 - 10.1126/sciadv.aaz0742
DO - 10.1126/sciadv.aaz0742
M3 - Article
C2 - 32537491
AN - SCOPUS:85086626320
SN - 2375-2548
VL - 6
JO - Science Advances
JF - Science Advances
IS - 23
M1 - eaaz0742
ER -