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Pitx1 directly modulates the core limb development program to implement hindlimb identity.
- Source :
-
Development (Cambridge, England) [Development] 2017 Sep 15; Vol. 144 (18), pp. 3325-3335. Date of Electronic Publication: 2017 Aug 14. - Publication Year :
- 2017
-
Abstract
- Forelimbs (FLs) and hindlimbs (HLs) 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. Here, we use expression profiling and analysis of direct Pitx1 targets to characterize the HL- and FL-restricted genetic programs in mouse and situate the Pitx1 -dependent gene network within the context of limb-specific gene regulation. We show that Pitx1 is a crucial 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 <superscript>-/-</superscript> 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 unique structural features of the limb.<br />Competing Interests: Competing interestsThe authors declare no competing or financial interests.<br /> (© 2017. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Base Sequence
Chondrogenesis genetics
Embryo, Mammalian metabolism
Enhancer Elements, Genetic genetics
Epigenesis, Genetic
Forelimb embryology
Forelimb metabolism
Gene Expression Regulation, Developmental
Gene Regulatory Networks
Genetic Loci
Genome
Homeodomain Proteins metabolism
Mice
SOX9 Transcription Factor metabolism
Hindlimb embryology
Hindlimb metabolism
Organogenesis genetics
Paired Box Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 144
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 28807899
- Full Text :
- https://doi.org/10.1242/dev.154864