Abstract
SummaryCaenorhabditis elegans seam cells divide in the stem-like mode throughout larval development, with the ability to both self-renew and produce daughters that differentiate. Seam cells typically divide asymmetrically, giving rise to an anterior daughter that fuses with the hypodermis and a posterior daughter that proliferates further. Previously we have identified rnt-1 (a homologue of the mammalian cancer-associated stem cell regulator Runx) as being an important regulator of seam development, acting to promote proliferation; rnt-1 mutants have fewer seam cells whereas overexpressing rnt-1 causes seam cell hyperplasia. We isolated the interacting CEH-20/Pbx and UNC-62/Meis TALE-class transcription factors during a genome-wide RNAi screen for novel regulators of seam cell number. Animals lacking wild type CEH-20 or UNC-62 display seam cell hyperplasia, largely restricted to the anterior of the worm, whereas double mutants have many additional seam cells along the length of the animal. The cellular basis of the hyperplasia involves the symmetrisation of normally asymmetric seam cell divisions towards the proliferative stem-like fate. The hyperplasia is completely suppressed in rnt-1 mutants, and rnt-1 is upregulated in ceh-20 and unc-62 mutants, suggesting that CEH-20 and UNC-62 function upstream of rnt-1 to limit proliferative potential to the appropriate daughter cell. In further support of this we find that CEH-20 is asymmetrically localised in seam daughters following an asymmetric division, being predominantly restricted to anterior nuclei whose fate is to differentiate. Thus, ceh-20 and unc-62 encode crucial regulators of seam cell division asymmetry, acting via rnt-1 to regulate the balance between proliferation and differentiation.
Highlights
Asymmetric cell divisions provide an important mechanism for the generation of cellular diversity during development and tissue regeneration
Summary Caenorhabditis elegans seam cells divide in the stem-like mode throughout larval development, with the ability to both selfrenew and produce daughters that differentiate
Seam cells typically divide asymmetrically, giving rise to an anterior daughter that fuses with the hypodermis and a posterior daughter that proliferates further
Summary
Asymmetric cell divisions provide an important mechanism for the generation of cellular diversity during development and tissue regeneration. In C. elegans the neuroectodermal seam cells provide a useful model for stem cell regulation. During larval development, they undergo reiterative asymmetric divisions in order to both selfrenew and differentiate into epidermal cells, neurons, glia and ray precursor cells of the male tail. The general pattern of division involves an asymmetric division at each larval stage, producing a posterior daughter that retains the ability to divide further and an anterior daughter that adopts a differentiated fate, most commonly contributing to epidermal tissue by fusing with the hyp syncytium (Sulston and Horvitz, 1977). There is a single symmetrical division at L2 in the V lineage, where both daughter cells retain proliferative ability and expand the pool of seam cells so that adult hermaphrodites have 16 seam nuclei per side
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