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Spatial regulation by multiple Gremlin1 enhancers provides digit development with cis-regulatory robustness and evolutionary plasticity.
- Source :
-
Nature communications [Nat Commun] 2021 Sep 21; Vol. 12 (1), pp. 5557. Date of Electronic Publication: 2021 Sep 21. - Publication Year :
- 2021
-
Abstract
- Precise cis-regulatory control of gene expression is essential for normal embryogenesis and tissue development. The BMP antagonist Gremlin1 (Grem1) is a key node in the signalling system that coordinately controls limb bud development. Here, we use mouse reverse genetics to identify the enhancers in the Grem1 genomic landscape and the underlying cis-regulatory logics that orchestrate the spatio-temporal Grem1 expression dynamics during limb bud development. We establish that transcript levels are controlled in an additive manner while spatial regulation requires synergistic interactions among multiple enhancers. Disrupting these interactions shows that altered spatial regulation rather than reduced Grem1 transcript levels prefigures digit fusions and loss. Two of the enhancers are evolutionary ancient and highly conserved from basal fishes to mammals. Analysing these enhancers from different species reveal the substantial spatial plasticity in Grem1 regulation in tetrapods and basal fishes, which provides insights into the fin-to-limb transition and evolutionary diversification of pentadactyl limbs.<br /> (© 2021. The Author(s).)
- Subjects :
- Animal Fins cytology
Animal Fins growth & development
Animals
Base Sequence
Biological Evolution
Boidae
Cattle
Chickens
Embryo, Mammalian
Embryo, Nonmammalian
Iguanas
Intercellular Signaling Peptides and Proteins metabolism
Limb Buds cytology
Limb Buds growth & development
Mice
Mice, Transgenic
Phylogeny
Protein Isoforms genetics
Protein Isoforms metabolism
Rabbits
Reverse Genetics methods
Sequence Alignment
Sequence Homology, Nucleic Acid
Sharks
Signal Transduction
Swine
Animal Fins metabolism
Enhancer Elements, Genetic
Gene Expression Regulation, Developmental
Intercellular Signaling Peptides and Proteins genetics
Limb Buds metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 34548488
- Full Text :
- https://doi.org/10.1038/s41467-021-25810-1