Making sense of neural development by comparing wiring strategies for seeing and hearing

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Science  08 Jan 2021:
Vol. 371, Issue 6525, eaaz6317
DOI: 10.1126/science.aaz6317

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Complex diversity from shared toolkits

Neural development builds diverse circuits out of a common toolkit, with shared mechanisms, transcription factors, and cellular signaling systems. Sitko and Goodrich compare and contrast the development of visual and auditory systems to parse the similarities in logic and the differences in sensory information processing.

Science, this issue p. eaaz6317

Structured Abstract


Since its infancy just over a century ago, the developmental neurobiology field has identified many unifying principles of neural circuit formation. We have come to appreciate the ways in which, for instance, transcriptional regulation of cell fate, molecular mechanisms of axon guidance and synapse formation, and activity-dependent refinement wire a variety of circuits across species. Certain systems, such as the vertebrate spinal cord or visual system, were historically popular choices for research because of their accessibility. Today, the field is poised to build on this foundation by studying how common mechanisms operate flexibly to assemble diverse circuits throughout the nervous system. By studying the fine details of how individual circuits acquire their characteristic features, we can learn more about the versatility and complexity of circuit assembly mechanisms and begin to unravel the rules that govern how and when certain strategies are used. To illustrate the value of such an approach, we present some examples of basic developmental events that unfold similarly and differently in the functionally specialized circuits for seeing and hearing, with a focus on the local circuitry and primary afferent projections of the vertebrate retina and cochlea.


Comparing and contrasting the development of retinal and cochlear circuitry in the context of each system’s functional demands reveals a common theme: Similar developmental events and strategies are evident in both circuits, but each system’s unique circuit features arise from relative differences in their reliance on those common mechanisms. For instance, neuronal heterogeneity and wiring complexity in the sense organ, as well as the number of central targets, are all relatively greater in the visual system than in the auditory system of vertebrates. As such, the retina relies heavily on neuronal identity–driven adhesion codes to assemble local synaptic connections among a large number of different neuronal subtypes. In turn, fasciculation plays a more prominent role in maintaining spatial relationships among cochlear afferents, whose identity is shaped by synaptic activity. The relative simplicity of wiring in the cochlea versus the retina parallels the computational handling in the two circuits: Both systems perform a combination of local and central computations to encode sensory stimuli, but more extensive parsing occurs locally in the retina than in the cochlea. Instead, auditory afferents project to the auditory brainstem and then arborize locally in their target to initiate a series of parallel computations. Within the different cellular contexts of these developing circuits, even the same molecules can mediate distinct functions. For example, canonical Eph/ephrin gradients guide retinotopic mapping, whereas in the cochlea, the same molecules mediate fasciculation and segregation of peripheral inputs. Therefore, the formation of topographic maps in the visual and auditory systems, although superficially similar, appears to rely on overlapping yet distinct mechanisms.


Although there is broad agreement about the basic development events that form a functional circuit, we remain unable to explain the wiring of any circuit completely. Looking forward, we need to define the full range of developmental strategies and identify points of flexibility that adapt each mechanism to specific wiring challenges. With the availability of sophisticated methods to visualize and manipulate developing circuits, today’s researchers are no longer limited to experimentally accessible systems and can characterize phenotypes with ever greater resolution and depth, from the position of an individual synapse to the effects of a single manipulation on the whole genome. By taking a deep dive into the contributions of supposedly well-understood developmental processes in circuits with fundamentally different architectures, we can reveal novel roles for familiar mechanisms and molecules, thereby expanding our knowledge of how dynamic and versatile strategies are harnessed to create the diverse circuits needed for complex behavior.

A balancing act: Wiring visual and auditory circuits.

(A and B) Afferent projections from the retina (A) and cochlea (B) initiate circuits for seeing and hearing. In both systems, sensory stimuli are encoded topographically. However, information from the two sides of the head (green and magenta) converges at different levels. D, dorsal; L, lateral. (C) Wiring features specialized to meet the specific functional demands of sight and hearing arise by common cellular and molecular strategies operating in different ways and to different extents.


The ability to perceive and interact with the world depends on a diverse array of neural circuits specialized for carrying out specific computations. Each circuit is assembled using a relatively limited number of molecules and common developmental steps, from cell fate specification to activity-dependent synaptic refinement. Given this shared toolkit, how do individual circuits acquire their characteristic properties? We explore this question by comparing development of the circuitry for seeing and hearing, highlighting a few examples where differences in each system’s sensory demands necessitate different developmental strategies.

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