Time of cell origin in the retina of the rhesus monkey (Macaca mulatta) was studied by plotting the number of heavily radiolabeled nuclei in autoradiograms prepared from 2- to 6-month-old animals, each of which was exposed to a pulse of 3H-thymidine (3H-TdR) on a single embryonic (E) or postnatal (P) day. Cell birth in the monkey retina begins just after E27, and approximately 96% of cells are generated by E120. The remaining cells are produced during the last (approximately 45) prenatal days and into the first several weeks after birth. Cell genesis begins near the fovea, and proceeds towards the periphery. Cell division largely ceases in the foveal and perifoveal regions by E56. Despite extensive overlap, a class-specific sequence of cell birth was observed. Ganglion and horizontal cells, which are born first, have largely congruent periods of cell genesis with the peak between E38 and E43, and termination around E70. The first labeled cones were apparent by E33, and their highest density was achieved between E43 and E56, tapering to low values at E70, although some cones are generated in the far periphery as late as E110. Amacrine cells are next in the cell birth sequence and begin genesis at E43, reach a peak production between E56 and E85, and cease by E110. Bipolar cell birth begins at the same time as amacrines, but appears to be separate from them temporally since their production reaches a peak between E56 and E102, and persists beyond the day of birth. Muller cells and rod photoreceptors, which begin to be generated at E45, achieve a peak, and decrease in density at the same time as bipolar cells, but continue genesis at low density on the day of birth. Thus, bipolar, Muller, and rod cells have a similar time of origin. The maximal temporal separation of cell birth is between cones and amacrine cells so that cell generation exhibits two relatively distinct phases: the first phase gives rise to ganglion, horizontal, and cone cells, and the second phase to amacrine, bipolar, rod, and Muller cells. In addition, cells of the first phase are generated faster than the second phase cells, and there are differences in the topography of spread of labeled cells between the two phases. Each cell class displays a central-to-peripheral gradient in genesis, although the spatiotemporal characteristics of the gradients differ between the classes.(ABSTRACT TRUNCATED AT 400 WORDS)

Cytogenesis in the monkey retina

Müller glia: Stem cells for generation and regeneration of retinal neurons in teleost fish.

Notch-Delta signaling is required for spatial patterning and Müller glia differentiation in the zebrafish retina.

The expression of two calcium-dependent adhesion molecules of the cadherin superfamily (cadherin-6B and cadherin-7) was mapped in the embryonic neural retina and retinofugal pathways of the chicken embryo and compared with the expression of R-cadherin, N-cadherin, and B-cadherin, studied previously Whereas B-cadherin is only found in Miller glia, the other four cadherins are each expressed by specific subpopulations of retinal neurons For example, different (but partly overlapping) populations of bipolar cells express R-cadherin, cadherin-6B, and cadherin-7 Cadherin-6B and cadherin-7 are also expressed by subsets of amacrine cells In the inner plexiform layer, cadherin-6B and cadherin-7 immunoreactivities are restricted to specific sublaminae associated with synapsin-I-positive nerve terminals In addition, cadherin-6B and cadherin-7 are expressed by a subset of ganglion cells that project to several retinorecipient nuclei forming part of the accessory optic system (eg, nucleus of the basal optic root and external pretectal nucleus) Together with their connecting fiber tracts, these nuclei also express cadherin-6B and cadherin-7 in their neurons and neuropile The expression patterns of the two cadherins overlap but show distinct differences Some other visual nuclei express cadherin-7 but not cadherin-6B The expression patterns differ from those previously described for N- and R-cadherin Together, these results demonstrate that cadherins could provide a system of adhesive cues that specify developing retinal circuits and other functional connections and subsystems in the embryonic chicken visual system

Cadherin expression in the retina and retinofugal pathways of the chicken embryo.

Tritiated thymidine studies suggest that Muller cells are the last cells born in the retina, although several authors describe Muller cells throughout the retina from very early ages. In this study immunohistochemistry was used to identify progenitor and Muller cells in human foetal retina. Antibodies to nestin (an intermediate filament protein expressed by neural progenitor cells), vimentin, cellular retinaldehyde binding protein (CRALBP) and glutamate and aspartate transporter (GLAST), which are each expressed by Muller cells, were used in combination with anti-Ki67 to identify proliferating cells. By definition, Ki67-positive proliferating cells were present in undifferentiated retina, but not in differentiated retina. Nestin-immunoreactive (IR) cells colocalized with vimentin throughout the retina. CRALBP-IR was detected in differentiated retina and in some proliferating cells. GLAST-IR cells were present only within the differentiated region. Nestin, vimentin and CRALBP each colocalized with mitotic Ki67-IR cells, suggesting that in foetal retina Muller cells and retinal progenitor cells are overlapping populations and that Muller cells are end-stage progenitor cells.

Müller cells express the neuronal progenitor cell marker nestin in both differentiated and undifferentiated human foetal retina.

The sequence of morphological differentiation of Muller cells in the chick retina was investigated in relation to the differentiation of the retinal neurons using the Golgi method. From the beginning of differentiation, the Muller cell develops spurs and lateral processes. Some of these glial processes become transformed into accessory prolongations of the Muller cell. From the 17th or 18th day of incubation, the morphology of the Muller cells is similar to that of the adult retina. On the basis of their inner prolongation, two types of Muller cells were identified. The first type, with diffuse and abundant descending processes, is identical to that described classically. The second type is a cell characterized by sparse and scanty inner ramifications.



This report also describes electron microscopic observations of Muller cells and their enwrapping relationship with the axons of the optic nerve fiber layer.

M. M. Magalhaes

Papers

Morphological differentiation of the Müller cell: Golgi and electron microscopy study in the chick retina.