Address for correspondence: Denis Thieffry, Laboratoire de Génétique et Physiologie du Développement, Parc Scientifique de Luminy, CNRS Case 907, 13288 Marseille cedex 9, France. Voice: (+33) 491 82 85 17; fax: (+33) 491 82 86 21.
thieffry{at}lgpd.univ-mrs.fr
Lucas Sánchez, Centro de Investigaciones Biológicas, Velázquez 144, 28006 Madrid, Spain. Voice: (+34) 91 564 4562, ext. 4322; fax: (+34) 91 562 7518.
lsanchez{at}cib.csic.es
Ann. N.Y. Acad. Sci. 981: 135-153 (2002).
Generally speaking, epigenetic states or epigenetic regulation
refer to situations in which several states of gene expression
may coexist in similar environmental conditions, despite the
absence of significant changes in the genomic sequence. In one
way or another, the mechanisms behind these phenomena involve
vicious circles, so that each epigenetic state tends to sustain
itself, even after the disappearance of the inductive signal
involved in the selection of that particular state. These vicious
circles constitute positive feedback circuits and are found
at the core of many developmental regulatory systems. In this
paper, we present a qualitative model for the regulatory network
formed by maternal and gap gene cross-regulations. This network
controls the initial anterior-posterior patterning during early
Drosophila embryogenesis and encompasses several intertwined
feedback circuits. On the basis of our model analysis, we derive
interesting insights about how specific expression states of
the gap genes are selected along the anterior-posterior axis,
in particular in relation with the activity of one positive
feedback circuit, namely that formed by
giant and
Krüppel cross-inhibitions. In addition, we are able to qualitatively
simulate the patterns of gene expression in the wild-type, as
well as to predict the phenotypes of various loss-of-function
mutations at the maternal and gap genes, or
cis-regulatory mutations
at the gap genes, as well as the effects of ectopic expression
of these genes.
