Proximo-distal positional information encoded by an Fgf-regulated gradient of homeodomain transcription factors in the vertebrate limb

Science Advances
Irene DelgadoMiguel Torres

Abstract

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.

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Citations

Sep 13, 2020·Development·Caitlin McQueen, Matthew Towers
Apr 20, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Carlos I Lorda-DiezJuan A Montero
May 30, 2021·Cells & Development·Neil Vargesson
Jun 15, 2021·Frontiers in Cell and Developmental Biology·María Beatriz Durán AlonsoThomas Schimmang
Jul 14, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Marc Fernandez-GuerreroMarian A Ros

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Datasets Mentioned

BETA
GSE134066

Methods Mentioned

BETA
immunoprecipitation
ChIPseq

Software Mentioned

ggplot2 R package
MATLAB
ImageJ
Plot Profile

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