Combinatorial Signaling in the Specification of Unique Cell Fates

Abstract

How multifunctional signals combine to specify unique cell fates during pattern formation is not well understood. Here, we demonstrate that together with the transcription factor Lozenge, the nuclear effectors of the EGFR and Notch signaling pathways directly regulate D-Pax2 transcription in cone cells of the Drosophila eye disc. Moreover, the specificity of D-Pax2 expression can be altered upon genetic manipulation of these inputs. Thus, a relatively small number of temporally and spatially controlled signals received by a set of pluripotent cells can create the unique combinations of activated transcription factors required to regulate target genes and ultimately specify distinct cell fates within this group. We expect that similar mechanisms may specify pattern formation in vertebrate developmental systems that involve intercellular communication.

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

“…This likely reflects the combinatorial nature of signaling in the regulation of cell fate (Flores et al, 2000;Sommer and Rao, 2002). Additionally, many other growth factor effects remain to be explored.…”

Crosstalk between the EGFR and other signalling pathways at the level of the global transcriptional corepressor Groucho/TLE

“…As mentioned above, target promoters frequently integrate distinct signals in the nucleus. A nice example for this is the expression of D-Pax2 in the Drosophila eye, that depends on the combined binding of effectors of both the N and EGFR pathways, together with tissue-specific transcription factors (Flores et al, 2000). Some of the intersections between signalling cascades might also occur via mutual cytoplasmic components.…”

Signal integration during development: Insights from the Drosophila eye

“…The role of Notch in cone cell development has been explored in detail in an elegant study by Banerjee and colleagues that initiated with the observation that loss of Notch signaling results in elimination of the cone cell marker D-Pax2 (Flores et al, 2000). The link between Notch activation and cone cell expression of D-Pax2 appears direct, because Su(H) can bind to a D-Pax2 control element (the sparkling minimal enhancer, or SME) in vitro and cone cell-specific transcription of D-Pax2 requires functional Su(H) binding sites in vivo.…”

“…The link between Notch activation and cone cell expression of D-Pax2 appears direct, because Su(H) can bind to a D-Pax2 control element (the sparkling minimal enhancer, or SME) in vitro and cone cell-specific transcription of D-Pax2 requires functional Su(H) binding sites in vivo. In addition to Notch, the EGFR pathway is also necessary for expression of D-Pax2 in cone cells (Flores et al, 2000). Temperaturesensitive inactivation of EGFR, expression of EGFR DN , expression of a constitutively active Yan repressor (Yan ACT ), or loss of pointed function all lead to the loss of D-Pax2 expression in the larval eye disc.…”

“…After the second mitotic wave, newly differentiating cells maintain Lz expression, where it participates in establishing cell type specific transcriptional programs (Flores et al, 1998(Flores et al, , 2000. For the presumptive R1 and R6, Lz is necessary for BarH1 expression (Daga et al, 1996).…”