“Fitness Fingerprints” Mediate Physiological Culling of Unwanted Neurons in Drosophila

Abstract

Our results show that the "Flower Code" is a general system to reveal cell fitness and that it may play similar roles in creating optimal neural networks in higher organisms. The Flower Code seems to be a more general mechanism for cell monitoring and selection than previously recognized.

Survival of the Fittest: Essential Roles of Cell Competition in Development, Aging, and Cancer

“…The fitness marker flower is required for the elimination of loser cells downstream of many competition scenarios in the wing disc [28]. Recently, flower was shown to be required for the elimination of neurons in the incomplete ommatidia of the developing Drosophila retina [2,[39][40][41]. This finding suggests that flower participates in the recognition and elimination of misconnected neurons.…”

“…Activation of Azot is set by the balance between [ 4 _ T D $ D I F F ] fwe fitness status and the level of the protective protein Sparc [33,48,49] ( Figure 1B). Altogether, this suggests that azot expression acts like a cell fitness checkpoint, integrating information from different fitness inputs [28,39,48] (Figure 1).…”

“…The fitness fingerprints are tissue-specific. For instance, expression of the loseA and loseB isoforms of fwe in a subset of cells is sufficient to induce their elimination in the Drosophila wing imaginal disc epithelia [28], while only the loseB isoform can induce loser status in neurons [33,39,42]. It has been recently shown that loser elimination correlates with the relative concentrations of fwe loseA or loseB isoforms in winner and loser cells, as well as the surface contact shared between winner and loser cells [45].…”

“…flower (fwe) encodes several isoforms that are used as 'fitness fingerprints' [39], which are necessary and sufficient to define winner/loser cell status and induce cell elimination downstream of several competition scenarios (low Myc, Minute À/+ , Scribble À/À , low Dpp). After recognition, cells that expose 'unfit fingerprints' at their membrane are eliminated from the tissue when contacting cells with 'fit fingerprints' ( Figure 1B).…”

Cell competition: how to eliminate your neighbours

“…2B, step 2) . Wg regulates expression of the Fwe Lose-B isoform during developmental cell death in the eye disc (Merino et al, 2013). In the future it will be important to determine whether this regulatory relationship exists in cell competition.…”