Migration and synaptogenesis of cone photoreceptors in the developing mouse retina

Abstract

Mouse retinal photoreceptor cell generation and morphogenesis take place in a well-characterized temporal sequence. Both rod and cone photoreceptor differentiation and synaptogenesis occur postnatally, but the relative timing of these events has been difficult to document due to the paucity of cell-specific markers. We have found that antibodies to neuron-specific enolase (NSE) preferentially label a subpopulation of photoreceptors in the outer nuclear layer (ONL) of the mouse retina in addition to labeling ganglion, amacrine, bipolar, and horizontal cells within the inner layers of the retina. The appearance of NSE immunoreactivity in the different classes of retinal neurons during development showed a close temporal relationship to the onset of expression of the synaptic vesicle-associated protein SV2 and clearly preceded the sequential development of synaptic connections in both inner and outer synaptic layers. The NSE-immunoreactive photoreceptors were identified as cones by dual labeling of their inner segments with the lectin peanut agglutinin or by colabeling with antisera to cone photopigments. Axonal extensions of NSE-labeled cone cells were shown to interact with those of differentiating horizontal cells as early as postnatal day 3 (P3). Colocalization of NSE with SV2 indicated that cone cells began to make synaptic contacts with horizontal cell processes several days prior to the development of rod synaptic terminals. Between P4 and P11, cone photoreceptor cell nuclei were observed to be scattered at various levels throughout the ONL and thus appeared to have become displaced from their previous position directly beneath the outer limiting membrane (OLM). By P12, the cone nuclei had migrated sclerad once again and were now observed to be neatly aligned adjacent to the OLM. In the rd mouse mutant, this migratory process was delayed, so that, at P12, positioning of the cone cell nuclei within the ONL was still quite irregular. Thus, we have identified a late migratory phase for cone photoreceptors during the second week after birth that correlates with the timing of maturation of the rod synaptic terminals just prior to eye opening. The types of cues used by maturing cone cells for their eventual sclerad location remain to be elucidated.

A Hybrid Photoreceptor Expressing Both Rod and Cone Genes in a Mouse Model of Enhanced S-Cone Syndrome

“…In addition, by P28, the M-opsin-positive cell bodies in rd7 appear to have relocated to their normal position at the scleral edge of the ONL (Figure S8). It is known that until P11, the cell bodies of cone photoreceptors in the mouse are normally dispersed throughout the ONL, only to relocate subsequently to the scleral edge of the ONL around P12 [23]. It is possible that in the rd7 mutant retina, there is a short delay in the relocation of the M-opsin–expressing cone cell bodies to the scleral edge of the ONL.…”

Zac1 functions through TGFβIIto negatively regulate cell number in the developing retina

“…Cones normally comprise only 3% of the murine photoreceptor pool [31]. In Zac1 +m/- +ECL and wild-type retinae, similar numbers of cones were labeled with peanut agglutinin (PNA; p = 0.26; wild type: 50.4 ± 1.2cells/field; n = 3; Zac1 +m/- +ECL: 64.6 ± 10.1cells/field; n = 3) and s-opsin ( p = 0.70; wild type: 44.22 ± 8.91cells/field; n = 3; Zac1 +m/- +ECL: 39.75 ± 6.66cells/field; n = 4; Additional data file 3 (g–j)).…”

The Development of Mid-Wavelength Photoresponsivity in the Mouse Retina

“…Cone photoreceptors begin to express markers of synaptic communication as early as P4 (41, 42) and synaptogenesis is mostly completed by eye-opening (43). The genes, presynaptic proteins, and ribbon synapses within cones reach functional levels of expression between P6-P10 (42-44).…”

“…The genes, presynaptic proteins, and ribbon synapses within cones reach functional levels of expression between P6-P10 (42-44). Connections between retinal ganglion cells and bipolar cells begin to form around P7 and mature in the third postnatal week (45-47).…”