The Ac/Sc proteins or by direct binding of E to common target genes. In a proneural cluster only cells that present the highest level of proneural proteins can escape inhibition by N signaling. The cells that escape the signal become a SOP and by lateral inhibition prevent the neighboring cells from acquiring the same fate. Proneural gene expression is under the control of enhancers that drive expression of both Ac and Sc in a proneural cluster. For instance the dorsocentral prepattern, is different from the scutellar prepattern. These specific enhancers mediating Sc self-stimulation play a central role in SOP determination. The EGFR signaling pathway plays an important role in macrochaete formation and is activated at different stage of the sensor organ development. The EGFR and Ras which transduces the pathway, positively interact in the proneural cluster that determines SOP emergence, restraining the N signal during macrochaete formation. Here we have investigated the function of the InR/FOXO pathway in bristle development and show that InR and FOXO are necessary for SOP determination, independently of the InR function in growth. A combined role of the EGFR/Ras pathway with the InR pathway is postulated. However the TOR pathway does not seem to be involved in the process Hexamethonium Bromide suggesting that InR/ FOXO acts on other target genes than on 4E-BP. We proposed a model in which the InR receptor plays a role in the development of the peripheral nervous system mainly through FOXO cell localization independently of its role in 20S-Notoginsenoside-R2 proliferation and apoptosis. The role of the InR/FOXO pathway appears early in PNS development before SOP formation. The use of different mutants involved in growth indicates that the TOR pathway does not play a major role in the phenotypes observed. Our results using genetic and molecular methods strongly suggest that InR/ FOXO controls the level of proneuronal genes such as ac, sc and Sens early in PNS development. This explains the interaction observed with N55e11. Several arguments indicate that the phenotypes observed when InR is overexpressed are not due, at least for the most part, to proliferation, growth or lack of apoptosis. First using anti-PH3 staining that allows to visualize mitotic cells, no extra mitoses are observed in the cluster. Overexpression of genes such as dE2F1, or dacapo did not lead to a significant increase or decrease in the number of macrochaetes. In addition co-expression of these genes with InR indicates no interaction. Moreover, the effects of InR and FOXO when overexpressed on respectively the increase and the decrease in cell number, could be estimated by the number of Acpositive cells in the DC and SC clusters. No significant differences were observed between the control and the overexpressed strain in the number of cells positive for Ac. If the possibility that proliferation is somehow involved in cluster size cannot be discarded, it does not account for the effects observed since the ratio of Sens-positive cells when InR is overexpressed over the control strain is much higher than the ratio of Ac-positive cells. A similar role for FOXO in apoptosis could also be discarded on the same basis. No clear interactions were observed between FOXO and genes involved in inhibition of apoptosis like diap1. Along the same line it has been shown by Bateman that the InR/TOR pathway plays a role in controlling the time of neural differentiation. This has been observed in photoreceptor formation but also in the chordotonal organs of the leg that develop on the same basis as thoracic bristles. The dynamic formation of the SOPs, particularly after a block of InR signaling was undertaken. No differences were observed before the end third larval instar in the test and in the overexpressed strain.