Describing the balance between cooperative binding and self-activation during pattern formation in Drosophila melanogaster. Francisco J P Lopes1,2, Alexander V Spirov3,4, Paulo M Bisch1. 1) Instituto de Biofisica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2) Polo de Xerem, Universidade Federal do Rio de Janeiro, Duque de Caxias, Brazil; 3) Laboratory of Evolutionary Modelling, the Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia; 4) Computer Science Department and Center of Excellence in Wireless & Information Technology, State University of New York at Stony Brook, Stony Brook, USA.
In Drosophila embryonic development, the gap gene hunchback (hb) is regulated in response to maternal signals like the antero-posterior gradient of Bicoid protein. This developmental gene has a strong anterior expression and a sharp on-off boundary at mid-embryo. Two major factors determine hb expression pattern: the cooperative binding of Bcd to the hb regulatory region and hb self-activation. A debate about the role of these mechanisms in the patterning of the hb sharp border has been established. Some experimental data indicate that Bcd cooperative binding would be sufficient for hb sharp border although some data indicate that hb self-activation could perform a critical role. In order to contribute to this discussion, we determined the Hill coefficient (nH) required for Bcd to generate the sharp border of Hb at different stages into cycle 14A [1]. We found that the nH ranges from 4 to 6 during the first half of cycle 14A and from 6 to 9 during the second half of this cycle. This result indicates that Bcd cooperative binding cannot account for hb sharpness at late embryos because this high nH is likely unachievable for Bcd binding to the hb promoter. To verify our results we estimated the nH required to pattern the Hb profile of 15 embryos expressing an hb14F allele that is defective in self-activation and found nH to be 3.0. Our results indicate that there are two different stages during hb pattern formation: a Bcd-dependent stage at early stages of cycle 14A and an Hb self-dependent stage at late stages of this cycle. [1] Lopes FJP, et al (2012). Developmental Biology 370(2): 165-172.