Open AccessPitx1 directly modulates the core limb development program to implement hindlimb identity
Author(s) -
Stephen Nemec,
Maëva Luxey,
Deepak Jain,
Aurélie Huang Sung,
Tomi Pastinen,
Jacques Drouin
Publication year - 2017
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.154864
Subject(s) - biology , limb development , transcription factor , genetics , gene , gene regulatory network , regulation of gene expression , gene expression profiling , microbiology and biotechnology , gene expression , computational biology
Forelimbs (FL) and hindlimbs (HL) develop complex musculoskeletal structures that rely on the deployment of a conserved developmental program. Pitx1, a transcription factor gene with expression restricted to HL and absent from FL, plays an important role in generating HL features. The genomic mechanisms by which Pitx1 effects HL identity remain poorly understood, however. Here, we use expression profiling and analysis of direct Pitx1 targets to characterize the HL- and FL-restricted genetic programs and situate the Pitx1-dependent gene network within the context of limb-specific gene regulation. We show that Pitx1 is a critical component of a narrow network of HL-restricted regulators, acting on a developmental program that is shared between FL and HL. Pitx1 targets sites that are in a similar chromatin state in FL and HL and controls expression of patterning genes as well as the chondrogenic program, consistent with impaired chondrogenesis in Pitx1-/- HL. These findings support a model in which multifactorial actions of a limited number of HL regulators redirect the generic limb development program in order to generate the limb's unique structural features.