Evolutionary Stability of Gene Regulatory Networks That Define the Temporal Identity of Neuroblasts

Abstract

The ensemble of gap genes is one of the best studied and most conserved gene regulatory networks (GRNs). Gap genes, such as hunchback (hb), Krüppel (Kr), pou-domain (pdm; pdm1 and pdm2), and castor (cas) genes belong to the well-known families Ikaros (IKZF1/hb), Krüppel-like factor (KLF/Kr), POU domain (BRN1/pdm-1, BRN2/pdm-2), and Castor homologs (CASZ1/cas), which are present in all vertebrate genomes and code for site-specific transcription factors. Gap genes form a core of an embryonic segmentation control subnetwork and define the temporal identity of neuroblasts in Drosophila embryos. The key gene regulatory mechanisms whereby the gap genes govern segmentation and neurogenesis are similar. Moreover, the gap genes are evolutionarily conserved in terms of their function as a core of the temporal specification GRN during neurogenesis in vertebrates, including humans. A problem of special interest is to understand the extent of conservation for the molecular mechanisms involved in the regulatory functions of the gap genes. The problem is especially important because human orthologs of the gap gens are crucial for many pathophysiological processes, including tumor growth suppression.