Complex interplay of three transcription factors in controlling the tormogen differentiation program of Drosophila mechanoreceptors

Abstract

We have investigated the expression and function of the Sox15 transcription factor during the development of the external mechanosensory organs of Drosophila. We find that Sox15 is expressed specifically in the socket cell, and have identified the transcriptional cis-regulatory module that controls this activity. We show that Suppressor of Hairless [Su(H)] and the POU-domain factor Ventral veins lacking (Vvl) bind conserved sites in this enhancer and provide critical regulatory input. In particular, we find that Vvl contributes to the activation of the enhancer following relief of Su(H)-mediated default repression by the Notch signaling event that specifies the socket cell fate. Loss of Sox15 gene activity was found to severely impair the electrophysiological function of mechanosensory organs, due to both cell-autonomous and cell-non-autonomous effects on the differentiation of post-mitotic cells in the bristle lineage. Lastly, we find that simultaneous loss of both Sox15 and the autoregulatory activity of Su(H) reveals an important role for these factors in inhibiting transcription of the Pax family gene shaven in the socket cell, which serves to prevent inappropriate expression of the shaft differentiation program. Our results indicate that the later phases of socket cell differentiation are controlled by multiple transcription factors in a collaborative, and not hierarchical, manner.

dbxmediates neuronal specification and differentiation through cross-repressive, lineage-specific interactions witheveandhb9

“…Moreover, hb9 and nkx6, which are expressed in nearly identical patterns of CNS neurons, also act redundantly to repress eve in a specific set of neurons (Broihier et al, 2004). Within the bristle lineage, the Su(H) and Sox15 transcription factors act redundantly in the socket cell to repress the expression of Shaven, a Pax-family transcription factor, thus restricting shaven expression to the sibling shaft cell (Miller et al, 2009). This event is crucial for socket cell differentiation, as derepression of shaven in the socket cell transforms socket cells towards shaft cells.…”

Notch-Independent Functions of CSL

“…In a cell with Notch signaling, NICD relieves the repression and permits the POU homeodomain factor Vvl to activate transcription. CSL and the POU factor interact with each other and cooperatively recognize a specific S þ POU binding motif (P) (Miller et al, 2009). (III) CSL repressor complex can bind the S motif to repress transcription.…”

Wg Signaling via Zw3 and Mad Restricts Self-Renewal of Sensory Organ Precursor Cells in Drosophila

“…Additional primary antibodies were the following: mouse E(Spl)M8 (Jennings et al 1994), mouse-cleaved Caspase-3 (Leinco), mouse pH3 (AbCam), rabbit lacZ (Organon Teknika), rabbit pMad-Gsk (Eivers et al 2009), guinea pig pMad-SSVS (Persson et al 1998; this is the well-known antibody against Receptor-phosphorylated Mad, which we distinguish from pMad-Gsk), guinea pig Sens (Nolo et al 2000), rat Su(H) (Gho et al 1996), guinea pig Sox15 and dPax2 (Miller et al 2009), rat Hairy (Kosman et al 1998), and rat Serrate (Papayannopoulos et al 1998). Secondary antibodies were goat anti-mouse, rabbit, rat, and guinea pig Alexa Fluor 488, -546, and -633 (Molecular Probes) and biotinylated goat anti-rabbit (Vector Labs).…”

“…Here these genes have the same spatial relationship, to each other and to the SOP markers Sens and Cut, as in larval wings (Ac is not expressed in prepupal wings; Figure S4). One unexpected finding was that the SOP lineage on the wing margin is not identical to the lineage of the notum: Sox15, a transcription factor marking the socket cell on the notum (Miller et al 2009), is not present in prepupal wings. As a result, we utilized Su(H) to mark the socket cell.…”

“…Along the posterior margin (Engrailed positive) Sens again acts as a proneural gene downstream of Wg and specifies a single row of non-innervated bristles on the margin (Jafer-Nejad et al 2003. The lineage that leads from a single Sens SOP to one type of adult sensory organ is well known: a mechanosensory notum bristle (Moore et al 2004;Miller et al 2009). In brief, notum bristle fate is initiated by Wg signals (Hayward et al 2008).…”