Abstract
Müller glia of the retina share many features with astroglia located throughout the brain including maintenance of homeostasis, modulation of neurotransmitter spillover, and robust response to injury. Here we present the molecular factors and signaling events that govern Müller glial specification, patterning, and differentiation. Next, we discuss the various roles of Müller glia in retinal development, which include maintaining retinal organization and integrity as well as promoting neuronal survival, synaptogenesis, and phagocytosis of debris. Finally, we review the mechanisms by which Müller glia integrate into retinal circuits and actively participate in neuronal signaling during development.
Highlights
Müller glia are the predominant synaptic astroglia of the retina
On the other hand, transforming growth factor β (TGFβ) secreted from neurons inhibits proliferation of Müller glial precursors in a manner that is antagonistic with epidermal growth factor (EGF) signaling (Close et al, 2005)
A recent study using single-cell RNA-sequencing revealed that the Notch-regulated nuclear factor 1 (NF1) transcription factors Nfia/b/x are enriched in late retinal progenitors and promote the formation of Müller glia and bipolar cells (Clark et al, 2019)
Summary
Müller glia are the predominant synaptic astroglia of the retina. They tile the entire tangential retinal plane and exhibit a radial morphology which traverses from photoreceptors to inner limiting membrane. Müller glia exhibit a strikingly complex morphology, with distinct membrane specializations that contact photoreceptor outer segments, neuronal somata within nuclear layers, neurites within synaptic layers, and blood vessels throughout the retina Their proximity to virtually every retinal cell type positions Müller glia ideally to guide the wiring and functioning of retinal circuits (Reichenbach and Bringmann, 2013). The two other retinal glial populations, astrocytes and microglia, migrate into the developing retina from other sources and play important developmental roles that are both distinct from and overlapping with those of Müller glia, as has been recently reviewed by other authors (Li et al, 2019; Dixon et al, 2021; Paisley and Kay, 2021) Following their birth, Müller glia begin to sculpt and integrate with nascent circuits as their morphological complexity grows and as they release molecules that are critical for neuronal survival and synaptogenesis (Reichenbach and Bringmann, 2013). We note that many recent studies have indicated a role for Müller glia in retinal regeneration by reprogramming gene expression (Goldman, 2014; Blackshaw and Sanes, 2021; Too and Simunovic, 2021) this will not be a focus of the present review
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