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Evolutionarily conserved developmental pathways

Cell survival: Epidermal growth factor and its receptor - the Ras pathway - ETS transcription factors

The Epidermal growth factor pathway is conserved across numerous and diverse species, from nematodes to humans. In Drosophila, EGF-R responds to the ligands Spitz and Argos. Whereas Spitz functions to enhance cell survival, Argos, an antagonist of EGF-R signaling, functions is a negative regulator of cell survival (Stemerdink, 1997). EGF-R targets ETS transcription factors during the induction of neural tissue promoting cell surivival. EGF-R signals through the Ras pathway, a highly conserved signal transduction pathway. MAPK (Rolled) is a component of the Ras pathway, is required at least three times in development: for the terminal system mediating responses to the Torso receptor, for neurogenic and wing vein pathways mediating responses to the EGF-receptor, and for the differentiation of photoreceptors, mediating responses to the Sevenless receptor. There is evidence that the interaction of ETS transcription factors with Serum response factor is also evolutionarily conserved. Human ETS transcription factors target cdc2, cyclinD1, c-fos, junB and prolactin. The Ras pathway functions to promote cell survival in radiation therapy (Pirollo, 1997), and genetic changes that constitutively activate intracellular survival pathways often occur in cancer (Eastman, 1995).

Drosophila                   Homologs in other species 
----------                   ----------------------------
Argos                        Other species: Epidermal growth factor

Spitz                        C. elegans: Lin-3
                             Mammalian: TGF-alpha, Epidermal growth factor

Epidermal growth factor      C. elegans: Let-23 
receptor                     Other species: Epidermal growth factor receptor

Ras Pathway components       Other species: Ras pathway components

Pointed                      C. elegans: Lin-1
                             Mammalian: Ets-1 and Ets-2

Yan                          C. elegans: Lin-1
                             Mammalian: Ets-1 and Ets-2

References

Eastman, A. (1995). Survival factors, intracellular signal transduction, and the activation of endonucleases in apoptosis. Semin. Cancer Biol. 6(1):45-52. Medline abstract: 96037775

Pirollo, K. F., Hao, Z., Rait, A,, Ho, C. W. and Chang, E. H. (1997). Evidence supporting a signal transduction pathway leading to the radiation-resistant phenotype in human tumor cells. Biochem. Biophys. Res. Commun. 230(1): 196-201. Medline abstract: 97148602

Stemerdink, C. and Jacobs, J. R. (1997). Argos and Spitz group genes function to regulate midline glial cell number in Drosophila embryos. Development 124(19): 3787-3796. Medline abstract: 98033257

date revised: 15 Nov 97

Developmental Pathways conserved in Evolution

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