Prdm13 is required for Ebf3+ amacrine cell formation in the retina

Abstract

Amacrine interneurons play a critical role in the processing of visual signals within the retina. They are highly diverse, representing 30 or more distinct subtypes. Little is known about how amacrine subtypes acquire their unique gene expression and morphological features. We characterized the gene expression pattern of the zinc-finger transcription factor Prdm13 in the mouse. Consistent with a developmental role, Prdm13 was expressed by Ptf1a+ amacrine and horizontal precursors. Over time, Prdm13 expression diverged from the transiently expressed Ptf1a and marked just a subset of amacrine cells in the adult retina. While heterogeneous, we show that most of these Prdm13+ amacrine cells express the transcription factor Ebf3 and the calcium binding protein calretinin. Loss of Prdm13 did not affect the number of amacrine cells formed during development. However, we observed a modest loss of amacrine cells and increased apoptosis that correlated with the onset timing of Ebf3 expression. Adult Prdm13 loss-of-function mice had 25% fewer amacrine cells, altered calretinin expression, and a lack of Ebf3+ amacrines. Forcing Prdm13 expression in retinal progenitor cells did not significantly increase amacrine cell formation, Ebf3 or calretinin expression, and appeared detrimental to the survival of photoreceptors. Our data show that Prdm13 is not required for amacrine fate as a class, but is essential for the formation of Ebf3+ amacrine cell subtypes. Rather than driving subtype identity, Prdm13 may act by restricting competing fate programs to maintain identity and survival.

Simultaneous deletion of Prdm1 and Vsx2 enhancers in the retina alters photoreceptor and bipolar cell fate specification, yet differs from deleting both genes

“…OTX2+ cells have the competence to become photoreceptors and bipolar cells, but some of these cells likely give rise to OTX2− amacrines and horizontals (Brzezinski et al, 2013;Brzezinski and Reh, 2015;Mills et al, 2017;Goodson et al, 2018) (Fig. 1A).…”

“…Both eyes were collected immediately after animal death and tissue collection followed our previous methods (Goodson et al, 2018). After fixing in 2% paraformaldehyde for 1-2 h at room temperature followed by a 10%, 20%, 30% sucrose gradient overnight, eyes were flash frozen in O.C.T.…”

Single cell transcriptomics reveals lineage trajectory of the retinal ganglion cells in wild-type andAtoh7-null retinas

“…Table 6). Examples of such genes included Sfrp2, Lhx2, Zfp36l1, and Vsx2 for RPCs (C0-C2) 14,[84][85][86] , Isl1, Nefl, Sncg, Gap43, and Ina for RGCs (C5 and C6) 22,49,60 , Thrb, Meis2, Prdm1, and Gngt2 for photoreceptors (C8 and C9) [87][88][89][90] , Tfap2a, Prdm13, and Onecut2 for amacrine and horizontal cell precursors (C7) 29,91,92 , and Ccnd2 and Msx1 for ciliary margin cells (C10) 93,93,94 .…”

Retinal development in mandarinfishSiniperca chuatsiand morphological analysis of the photoreceptor layer

“…Cone cells are responsible for distinguishing fine geometric structures and detailed colour information of object images, while rod cells are responsible for the capturing of light information in dim light conditions (Caves et al, ; Evans & Browman, ; Ueno et al, ). Inner nuclear cells, such as bipolar cells, are information bridges that connect photoreceptor and ganglion cells and the horizontal and amacrine cells play important roles in the horizontal processing of visual signals (Douglas & Partridge, ; Evans & Browman, ; Goodson et al, ). Specifically, ganglion cells are responsible for integrating signals from photoreceptors (Cook & Becker, ; Mack et al, ).…”