Abstract
ABSTRACTPatterning of a continuously growing naive field in the context of a life-long growing organ such as the teleost eye is of high functional relevance. Intrinsic and extrinsic signals have been proposed to regulate lineage specification in progenitors that exit the stem cell niche in the ciliary marginal zone (CMZ). The proper cell-type composition arising from those progenitors is a prerequisite for retinal function. Our findings in the teleost medaka (Oryzias latipes) uncover that the Notch-Atoh7 axis continuously patterns the CMZ. The complement of cell types originating from the two juxtaposed progenitors marked by Notch or Atoh7 activity contains all constituents of a retinal column. Modulation of Notch signalling specifically in Atoh7-expressing cells demonstrates the crucial role of this axis in generating the correct cell-type proportions. After transiently blocking Notch signalling, retinal patterning and differentiation is re-initiated de novo. Taken together, our data show that Notch activity in the CMZ continuously structures the growing retina by juxtaposing Notch and Atoh7 progenitors that give rise to distinct complementary lineages, revealing coupling of de novo patterning and cell-type specification in the respective lineages.
Highlights
The central nervous system (CNS) presents an extraordinary diversity of neuronal cell types
The retina, even though it is part of the CNS, has a relatively simple cellular composition, which has been extensively studied (Bassett and Wallace, 2012). It consists of six neuronal cell types and one glial cell type, which are distributed into three nuclear layers: the outer nuclear layer (ONL) containing the rod and cone photoreceptors (PRCs); the inner nuclear layer (INL) where bipolar cells (BCs), amacrine cells (ACs), horizontal cells (HCs) and Müller glia (MG) cells are located; and the ganglion cell layer (GCL) where the retinal ganglion cells (RGCs) as well as some ACs reside
Expression of Notch pathway components has been reported in the ciliary marginal zone (CMZ) of lifelong-growing organisms such as Xenopus and zebrafish (Dorsky et al, 1997; Raymond et al, 2006), its role in the continuous establishment of regularly patterned 3D neural columns of retinal cell types during continuous growth in the post-embryonic retina had not been addressed so far
Summary
The central nervous system (CNS) presents an extraordinary diversity of neuronal cell types. The retina, even though it is part of the CNS, has a relatively simple cellular composition, which has been extensively studied (Bassett and Wallace, 2012). It consists of six neuronal cell types and one glial cell type, which are distributed into three nuclear layers: the outer nuclear layer (ONL) containing the rod and cone photoreceptors (PRCs); the inner nuclear layer (INL) where bipolar cells (BCs), amacrine cells (ACs), horizontal cells (HCs) and Müller glia (MG) cells are located; and the ganglion cell layer (GCL) where the retinal ganglion cells (RGCs) as well as some ACs reside.
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