Document Type

Article

Publication Date

9-21-2021

Publication Title

Nat Commun

Keywords

JMG

JAX Source

Nat Commun 2021 Sep 21; 12(1):5557

Volume

12

Issue

1

First Page

5557

Last Page

5557

ISSN

2041-1723

PMID

34548488

DOI

https://doi.org/10.1038/s41467-021-25810-1

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.

Comments

This article is licensed under a Creative Commons Attribution 4.0 International License.

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