Downstream targets of Isl1 in the hindlimb field and genital tubercle

ABSTRACT: Despite the incredible morphological diversity found within vertebrates, embryonic development is often regulated by shared foundational mechanism maintained from a common ancestor. For instance, the tetrapod limb displays tremendous variation in size and shape but largely develops according to conserved gene regulatory networks, including signaling pathways, transcription factors, and enhancers. The phallus of amniotes is also thought to share a basic homology originating from their last common ancestor over 300 million years ago. The genital tubercle (GT) of mammals – the embryonic precursor to the penis and clitoris – shows similarities with the external genitalia of other amniotes prior to sexual differentiation. Many genes and enhancers show a common role in both the limbs and the external genitalia, and disruption of these loci can cause aberrant phenotypes in both structures. Among these shared limb-genital genes is Isl1. The Isl1 gene encodes a homeodomain transcription factor that is required for initiation of the hindlimb bud and for normal GT development. This study uses a combination of RNA-seq, ChIP-seq, and comparative genomics to identify potential targets of ISL1 during both hindlimb initiation and GT outgrowth. ChIP-seq data from mouse, chick, and other species reveals targets that are likely conserved from the last common ancestor of amniotes. A subset of ISL1 targets are shared between the hindlimb and the external genitalia, supporting the hypothesis that aspects of phallus development were coopted from the limb gene regulatory network. This systematic investigation of ISL1 transcriptional targets expands our knowledge of Isl1’s role in appendage development and generates further testable hypotheses concerning the establishment of these structures.

ORGANISM(S): Mus musculus Alligator mississippiensis Anolis sagrei Trachemys scripta Gallus gallus

PROVIDER: GSE202285 | GEO | 2025/04/04

REPOSITORIES: GEO