Topological Determinants of Gene Regulatory Networks and Their Role in Vertebrate Ontogenetic Constraints: A Systems Biology Perspective

Abstract

This review explores the intersection of developmental biology and differential topology in understanding vertebrate ontogenetic constraints. We examine how the topological organization of gene regulatory networks (GRNs) influences developmental trajectories and evolutionary possibilities. By analyzing the mathematical frameworks of differential topology and their application to chromatin architecture, we demonstrate how spatial gene arrangements create constraints that both channel and limit morphological evolution. Special attention is paid to the role of topologically associating domains (TADs) and their conservation across vertebrate lineages, suggesting their fundamental importance in maintaining developmental stability. We propose that the hierarchical nature of GRN topology serves as a primary mechanism for establishing evolutionary constraints while simultaneously facilitating phenotypic innovation within defined parameters. This synthesis provides new insights into how physical genome organization shapes the possibilities and limitations of vertebrate body plan evolution.