Cell proliferation control by Notch signalling during imaginal discs development in Drosophila

Abstract

The Notch signalling pathway is evolutionary conserved and participates in numerous developmental processes, including the control of cell proliferation. However, Notch signalling can promote or restrain cell division depending on the developmental context, as has been observed in human cancer where Notch can function as a tumor suppressor or an oncogene. Thus, the outcome of Notch signalling can be influenced by the cross-talk between Notch and other signalling pathways. The use of model organisms such as Drosophila has been proven to be very valuable to understand the developmental role of the Notch pathway in different tissues and its relationship with other signalling pathways during cell proliferation control. Here we review recent studies in Drosophila that shed light in the developmental control of cell proliferation by the Notch pathway in different contexts such as the eye, wing and leg imaginal discs. We also discuss the autonomous and non-autonomous effects of the Notch pathway on cell proliferation and its interactions with different signalling pathways.

Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle

“…Notch signalling controls cell growth and proliferation in several tissues during normal development, including imaginal discs [ 15 ] or T-cells [ 28 ], and overactivation of the Notch pathway leads to pathophysiological conditions such as wing disc hyperplasia [ 24 ] or tumour development [ 17 , 29 ]. Could Notch-dependent upregulation of metabolic genes help to stimulate tissue growth?…”

“…As the growth of the wing disc is dependent on Notch signalling [ 15 ] and we showed that Notch controls the expression of metabolic genes in this tissues ( figure 5 b–e ), we asked whether downregulation of metabolic genes would lead to smaller growth of the wing disc. Simultaneous downregulation of Hex-A and Impl3 or Impl3 and Glut1 using en -Gal4 driver caused significant reduction of the posterior compartment ( figure 5 h ), similar to the phenotype observed when downregulating Notch signalling [ 31 ].…”

“…The Notch signalling pathway regulates cell fate determination during development and it is also known to promote cell growth and division [ 15 ]. It can function as both a tumour suppressor and a tumour-promoting factor in several types of haematopoietic cancers and solid tumours [ 16 ].…”

Histidine is selectively required for the growth of Myc‐dependent dedifferentiation tumours in the Drosophila CNS

“…To investigate tissue-of-origin effects on histidine sensitivity, we compared N ACT clones in the CNS with those in the epithelium of the eye imaginal disc (Baonza & Garcia-Bellido, 2000;Brumby, 2003;Estella & Baonza, 2015). We observed that the growth of N ACT clones in the eye discs which exhibited dependency on Myc was also significantly decreased by Hdc knockdown (Fig EV4D-G).…”

Drosophila as a Model to Study the Link between Metabolism and Cancer

“…The Notch signalling pathway regulates cell proliferation and differentiation, and has been shown to function as both an oncogene or as a tumor suppressor [ 24 , 25 ]. Notch behaves as an oncogene in the Drosophila imaginal discs, in which Notch activation leads to tissue hyperplasia and tumor formation [ 26 ].…”