Abstract
Regeneration involves precise control of cell fate to produce an appropriate complement of tissues formed within a blastema. Several chromatin‐modifying complexes have been identified as required for regeneration in planarians, but it is unclear whether this class of molecules uniformly promotes the production of differentiated cells. We identify a function for p66, encoding a DNA‐binding protein component of the NuRD (nucleosome remodeling and deacetylase) complex, as well as the chromodomain helicase chd4, in suppressing production of photoreceptor neurons (PRNs) in planarians. This suppressive effect appeared restricted to PRNs because p66 inhibition did not influence numbers of eye pigment cup cells (PCCs) and decreased numbers of brain neurons and epidermal progenitors. PRNs from p66(RNAi) animals differentiated with some abnormalities but nonetheless produced arrestin+ projections to the brain. p66 inhibition produced excess ovo+otxA+ PRN progenitors without affecting numbers of ovo+otxA− PCC progenitors, and ovo and otxA were each required for the p66(RNAi) excess PRN phenotype. Together these results suggest that p66 acts through the NuRD complex to suppress PRN production by limiting expression of lineage‐specific transcription factors.
Highlights
Regeneration requires precise control of cell differentiation in order to build tissues with appropriate composition matched to those regions damaged by injury
The nucleosome remodeling and deacetylase (NuRD) complex is a conserved multi-subunit protein assembly that generally functions as a transcriptional repressor by linking detection of methylated DNA by methyl binding proteins to chromatin remodelers (Mi-2/CHD3/4) and histone deacetylases (HDAC1/2) (Torchy et al 2015). p66 is another core component of NuRD identified through biochemical purifications of both Xenopus and mammalian extracts (Brackertz et al 2002; Feng et al 2002) and contains a GATA-type zinc finger domain likely involved in sequence-specific DNA binding to assist targeting NuRD to specific loci (Feng et al 2002)
Together these results suggest that P66 acting through NuRD has a suppressive function in eye differentiation and that chromatin-remodeling factors can negatively regulate differentiated cell numbers in regeneration
Summary
Regeneration requires precise control of cell differentiation in order to build tissues with appropriate composition matched to those regions damaged by injury. Keywords Differentiation, eye regeneration, neoblasts, NuRD complex, p66, photoreceptor neurons, planarian, stem cells
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