Comments on the Hox timer and related issues

2024 not only marked the 100th anniversary of the discovery of the organizer by Hilde Pröscholdt-Mangold and Hans Spemann, but also the 40th anniversary of the discovery of the homeobox, a DNA region encoding a DNA binding peptide present in several transcription factors of critical importance for the gastrulating embryo. In particular, this sequence is found in the 39 members of the amniote Hox gene family, a series of genes activated in mid-gastrulation and involved in organizing morphologies along the extending anterior to posterior (AP) body axis. Over the past 30 years, the study of their coordinated regulation in various contexts has progressively revealed their surprising regulatory strategies, based on mechanisms acting in-cis, which can translate a linear distribution of series of genes along the chromatin fiber into the proper sequences of morphologies observed along our various body axes. The first regulatory layer is controlled by the Hox timer, a mechanism implementing a time-sequenced activation of these genes following their chromosomal order. Here, we discuss various aspects of this mechanism, emphasizing some of its singularities.