Recurrent hypermotif regulatory circuits in developmental programs.

Authors

Miri Adler, Ruslan Medzhitov

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 41. Pages e2538056123. Oct 13, 2026. Epub Oct 05, 2026.

Abstract

During development, cells self-organize into complex spatial and temporal patterns driven by regulatory circuits of transcription factors and morphogen signaling. However, the principles that govern these regulatory interactions remain poorly understood. Here, we introduce a framework to dissect the building-block circuits of developmental gene regulatory networks and explore their integration into higher-order hypermotif circuits. Using single-cell RNA-sequencing data spanning human intestinal development, we identify five recurrent network motifs, including feedforward and feedback loops, and investigate their roles in the regulation of gene expression. Our analysis reveals distinct categories of developmental genes based on their roles within network motifs, highlighting major transitions in regulatory architecture across developmental stages. Furthermore, we model the emergent dynamical properties of hypermotif circuits, including their potential roles in regulating morphogen signaling. This study uncovers a common theme in regulatory circuits of developmental programs, emphasizing how the combinatorial wiring of regulatory motifs enables robust and diverse tissue formation.

PMID:
42832665
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.

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