Molecular Genetics of Axial Patterning, Growth and Disease in Drosophila Eye by Unknown

Author:Unknown
Language: eng
Format: epub
ISBN: 9783030422462
Publisher: Springer International Publishing

Because Bar is important for maintenance of the undifferentiated state of the basal cells, spatial and temporal regulation of Bar expression is crucial for proper eye development. Consistent with the Bar function that represses the Ato expression, Bar and Ato expression shows a complementary pattern with a sharp boundary between the Bar+ and Ato+ cells along the posterior edge of the furrow. This pattern of Bar expression is regulated by multiple pathways depending on time and position in the disc (Fig. 3) (Lim and Choi 2004). Prior to furrow initiation and Ato expression, Bar appears to be induced by secreted factors from the posterior margin of the disc. For example, Hh is one of the first secreted factor expressed in the posterior margin at the time of furrow initiation, and it has been shown that Hh signaling is in part responsible for initial Bar induction (Lim and Choi 2004). Evidence also suggests that Bar is induced by several factors functioning in the furrow. Immediately behind the furrow, Bar expression depends on EGFR signaling which is induced by Ato expression in the intermediate groups (Fig. 3).

An important function of Ato is to regulate its own expression. Ato protein induced by activation of the 3′ regulatory region can turn on itself by binding to its own 5′ regulatory region (Sun et al. 1998). Interestingly, TRAP (thyroid hormone receptor associated proteins) /mediator complex is involved in the regulation of ato expression in the proneural groups. The TRAP complex acts as a coactivator for a variety of transcriptional activators (Ito and Roeder 2001; Malik and Roeder 2000). Among many mediator complex proteins, two Drosophila TRAPs, Kohtalo (Kto, TRAP230) and Blind spot (Bli, also called Skuld, TRAP240), have been extensively studied for their roles in retinal neurogenesis. In TRAP mutant clones, Ato is ectopically induced behind the furrow (Treisman 2001).

In contrast, TRAPs are required for ato expression in the intermediate groups. Because Ato expression in the intermediate groups is dependent on Ato itself, it is possible that TRAP complex might act as coactivator for Ato. Indeed, in the absence of TRAP, Ato fails to induce EGFR signaling and Sca expression that are necessary for lateral inhibition, thus resulting in ectopic Ato expression. Likewise, Kto and Skd are also required for positive Ato functions to induce Ato targets such as Ato itself and Senseless (Sens) within the proneural clusters. Hence, TRAP complex is required for Ato expression and other Ato target genes such as sca, sens, and rho in the intermediate groups (Fig. 4) (Lim et al. 2007).

Fig. 4A model of TRAP-mediated Ato activation in early retinal neurogenesis. Kto (TRAP230) and Skd (TRAP240) function as coactivators for Ato in the proneural clusters and are therefore required for expression of Ato target genes such as Ato itself, Sens, Sca, and for activation of EGFR signaling. Ato and Sens are required for selection and differentiation of the R8 founder neurons. In contrast, EGFR signaling and Sca are involved in repressing Ato expression in cells between proneural clusters. Kto/Skd

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