Disappearance of Temporal Collinearity in Vertebrates and Its Eventual Reappearance

Abstract

Simple Summary In 1999 T. Kondo and D. Duboule performed excisions of posterior upstream DNA domains in mouse embryos and they observed that for an extended excision (including Evx gene) the Hox genes of the cluster were simultaneously expressed with the first Hoxd1 gene ‘as if’ Temporal Collinearity (TC) had disappeared. According to a Biophysical Model (BM) during Hox gene expression, Hox clusters behave similar toexpanding elastic springs. For the extended upstream DNA excision, BM predicts the TC disappearance and an experiment is proposed to test this BM prediction. In the chick limb bud C. Tickle et al. observed that the excision of the apical ectodermal ridge (AER) caused the inhibition of HoxA13 expression. However, the implantation of FGF soaked beads at the tip of the limb could surprisingly rescue HoxA13 expression after 24 h so that TC is restored.Brachyury transcription factor (TF) is essential in identifying the targets of this transcription and a chromatin immunoprecipitation microarray chip (ChIP-chip) was produced which can be inserted in the mouse embryonic cells. It is here proposed to insert this chip in the mutant cells where TC has disappeared and compare it to the limb bud case.Is TC restored? It is an important issue worth exploring. Abstract It was observed that a cluster of ordered genes (Hox1, Hox2, Hox3…) in the genome are activated in the ontogenetic units (1, 2, 3 …) of an embryo along the Anterior/Posterior axis following the same order of the Hox genes. This Spatial Collinearity (SC) is very strange since it correlates events of very different spatial dimensions. It was later observed in vertebrates, that, in the above ordering, first is Hox1expressed in ontogenetic unit 1, followed later by Hox2 in unit 2 and even later Hox3 in unit 3. This temporal collinearity (TC) is an enigma and even to-day is explored in depth. In 1999 T. Kondo and D. Duboule, after posterior upstream extended DNA excisions, concluded that the Hox cluster behaves ‘as if’ TC disappears. Here the consideration of TC really disappearing is taken face value and its repercussions are analyzed. Furthermore, an experiment is proposed to test TC disappearance. An outcome of this experiment could be the reappearance (partial or total) of TC.