title: The zebrafish flotte lotte mutant reveals that the local retinal environment promotes the differentiation of proliferating precursors emerging from their stem cell niche.
abstract: It is currently unclear how intrinsic and extrinsic mechanisms cooperate to control the progression from self-renewing to neurogenic divisions in retinal precursor cells. Here, we use the zebrafish flotte lotte (flo) mutant, which carries a mutation in the elys (ahctf1) gene, to study the relationship between cell cycle progression and neuronal differentiation by investigating how proliferating progenitor cells transition towards differentiation in a retinal stem cell niche termed the ciliary marginal zone (CMZ). In zebrafish embryos without Elys, CMZ cells retain the capacity to proliferate but lose the ability to enter their final neurogenic divisions to differentiate as neurons. However, mosaic retinae composed of wild-type and flo cells show that despite inherent cell cycle defects, flo mutant cells progress from proliferation to differentiation when in the vicinity of wild-type retinal neurons. We propose that the differentiated retinal environment limits the proliferation of precursors emerging from the CMZ in a manner that explains the spatial organisation of cells in the CMZ and ensures that proliferative retinal progenitors are driven towards differentiation.
authors.affiliation: Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E6BT, UK.
authors.forename: Kara L
authors.initials: KL
authors.lastname: Cerveny
authors.forename: Florencia
authors.initials: F
authors.lastname: Cavodeassi
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Turner
authors.forename: Tanya A
authors.initials: TA
authors.lastname: de Jong-Curtain
authors.forename: Joan K
authors.initials: JK
authors.lastname: Heath
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wilson
mesh_terms: D000818:Animals; D017209:Apoptosis; D005246:Feedback; D055495:Neurogenesis; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D012160:Retina / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C533929:AHCTF1 protein, zebrafish; D028861:Nuclear Pore Complex Proteins; D029961:Zebrafish Proteins