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Abstract: The dendritic arbors of neurons are organized into unique spatial patterns that are well suited for their specific functions. Although the intracellular signaling pathways that determine dendritic arbor size and branching patterns during development are not completely understood, it is evident that neurotransmission-mediated elevation in intracellular calcium levels ([Ca2+]i) plays a major role. Recent advances in calcium imaging and genetic approaches have provided new insight into how calcium acts to regulate dendritic growth and remodeling. Global increases in [Ca2+]i that occur upon neuronal depolarization control dendritic arbor growth by regulating transcription. However, the detailed branching patterns of dendritic arbors are regulated by local calcium signaling. Calcium-induced calcium release (CICR) from intracellular stores acts to locally stabilize dendritic branches, presumably triggered by neurotransmission upon contact with newly established inputs. The effects of global and local increases in [Ca2+]i on dendritic structure are cell type- and age-dependent. Unraveling the signaling pathways evoked by local and global rises in [Ca2+]i that shape the developing dendritic arbor at each developmental stage remains challenging but highly important. [Copyright &y& Elsevier]

Summary Sensory processing can be tuned by a neuron's integration area, the types of inputs, and the proportion and number of connections with those inputs. Integration areas often vary topographically to sample space differentially across regions. Here, we highlight two visual circuits in which topographic changes in the postsynaptic retinal ganglion cell (RGC) dendritic territories and their presynaptic bipolar cell (BC) axonal territories are either matched or unmatched. Despite this difference, in both circuits, the proportion of inputs from each BC type, i.e., synaptic convergence between specific BCs and RGCs, remained constant across varying dendritic territory sizes. Furthermore, synapse density between BCs and RGCs was invariant across topography. Our results demonstrate a wiring design, likely engaging homotypic axonal tiling of BCs, that ensures consistency in synaptic convergence between specific BC types onto their target RGCs while enabling independent regulation of pre- and postsynaptic territory sizes and synapse number between cell pairs. Graphical Abstract Highlights • Bipolar cells (BCs) and ganglion cells (GCs) can vary topographically in size • Changes in BC size do not always scale with that of their postsynaptic GCs • Proportion of synapses from each BC type with partner GC is invariant of location • BC axonal tiling promotes maintenance of stereotypic BC-GC connectivity patterns Yu et al. show that the density of excitatory synapses on retinal output neurons is invariant of retinal location, even though connectivity between pre- and postsynaptic cell pairs can vary. These results have implications for understanding topographic variations in processing of visual stimuli and for understanding consistency of CNS wiring diagrams. [ABSTRACT FROM AUTHOR]

Summary Clinical and genetic heterogeneity associated with retinal diseases makes stem-cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 136. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared with peripheral retina. Human and mouse retinal transcriptomes show remarkable similarity in developmental stages, although morphogenesis was greatly expanded in humans. Integration of DNA accessibility data allowed us to reconstruct transcriptional networks controlling photoreceptor differentiation. Our studies provide insights into human retinal development and serve as a resource for molecular staging of human stem-cell-derived retinal organoids. [ABSTRACT FROM AUTHOR]