CEH-20/Pbx and UNC-62/Meis function upstream of rnt-1/Runx to regulate asymmetric divisions of the C. elegans stem-like seam cells

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作者：

S Hughes，C Brabin，PJ Appleford，A Woollard

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摘要：

Caenorhabditis elegansseam 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 identifiedrnt-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-1mutants have fewer seam cells whereas overexpressingrnt-1causes 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 inrnt-1mutants, andrnt-1is upregulated inceh-20andunc-62mutants, suggesting that CEH-20 and UNC-62 function upstream ofrnt-1to 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-20andunc-62encode crucial regulators of seam cell division asymmetry, actingvia rnt-1to regulate the balance between proliferation and differentiation.

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关键词：

C. elegans Seam cell Asymmetric cell division ceh-20/Pbx unc-62/Meis rnt-1/Runx

DOI：

10.1242/bio.20134549

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年份：

2013