Molecular Biology

A. Simeone, D. Acampora, V. Nigro, A. Faiella, M. D'Esposito, A. Stornainolo, et al., "Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells," Mechanisms of Development, 33:215-228, 1991. Edoardo Bonicelli (H. S. Raffaele, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy): "

October 26, 1992

A. Simeone, D. Acampora, V. Nigro, A. Faiella, M. D'Esposito, A. Stornainolo, et al., "Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells," Mechanisms of Development, 33:215-228, 1991.

Edoardo Bonicelli (H. S. Raffaele, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy): "This paper put some order into the zoo of vertebrate homeobox genes controlling positional information necessary for the appropriate body structures to develop along the major body axis. The process of putting these homeobox genes into order involved two steps.

"First, we completed the inventory of the existing 38 HOX genes, belonging to 13 homology groups and located in four genomic loci- -HOX1 to HOX4. In humans, HOX1 contains 11 genes found in 110 kilobases of chromosome 7; HOX2 contains nine genes in 100 kb of chromosome 17; HOX3 contains nine genes in 120 kb of chromosome 12; and HOX4 contains nine genes in 110 kb of chromosome 2. This confirmed and extended the concept of `structural colinearity' between the position of 3e to 5e of single genes along a given HOX locus and the location anterior to posterior of the developing body regions they control.

"Second, with this paper we also introduced the concept of `temporal colinearity.'

"We and others had already observed that retinoic acid specifically induces HOX gene expression in the embryonal carcinoma cells, which provide an interesting in vitro model to study the molecular events in development.

"In this paper, we showed that these HOX genes are activated in a sequential order, in the 3e to 5e direction, along each locus. Activation of early responding genes requires a few minutes of treatment with retinoic acid, whereas full activation of late responding genes requires more than a week of treatment.

"Sequential activation of these genes in a temporal order colinear with both their 3e to 5e localization in the locus and the spatially restricted expression pattern along the embryonic anterior-posterior body axis was subsequently observed in both frog and mouse embryos. In this way, the paradigm of temporal colinearity of HOX genes was definitely established.

"According to some authors, it is, indeed, the temporal colinearity and not the structural colinearity that really matters for the very development of vertebrates."


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