Wiring the Brain: The Biology of Neuronal Guidance

Chédotal, Alain; Richards, Linda J.

doi:10.1101/cshperspect.a001917

Cited by 142 publications

(108 citation statements)

References 151 publications

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“…For simplicity, we chose chemical gradients as classic developmental cues (Sperry, 1963) and allowed each neuron to grow its axons independently. This is not what happens in life, where neurons differentiate in a defined dorsoventral and headto-tail sequence (Lewis, 2006;Chédotal and Richards, 2010). As a result, the axons of more precocious neurons can be followed by fasciculation of those that develop later.…”

Section: Discussionmentioning

confidence: 98%

Can Simple Rules Control Development of a Pioneer Vertebrate Neuronal Network Generating Behavior?

et al. 2014

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How do the pioneer networks in the axial core of the vertebrate nervous system first develop? Fundamental to understanding any full-scale neuronal network is knowledge of the constituent neurons, their properties, synaptic interconnections, and normal activity. Our novel strategy uses basic developmental rules to generate model networks that retain individual neuron and synapse resolution and are capable of reproducing correct, whole animal responses. We apply our developmental strategy to young Xenopus tadpoles, whose brainstem and spinal cord share a core vertebrate plan, but at a tractable complexity. Following detailed anatomical and physiological measurements to complete a descriptive library of each type of spinal neuron, we build models of their axon growth controlled by simple chemical gradients and physical barriers. By adding dendrites and allowing probabilistic formation of synaptic connections, we reconstruct network connectivity among up to 2000 neurons. When the resulting "network" is populated by model neurons and synapses, with properties based on physiology, it can respond to sensory stimulation by mimicking tadpole swimming behavior. This functioning model represents the most complete reconstruction of a vertebrate neuronal network that can reproduce the complex, rhythmic behavior of a whole animal. The findings validate our novel developmental strategy for generating realistic networks with individual neuron-and synapse-level resolution. We use it to demonstrate how early functional neuronal connectivity and behavior may in life result from simple developmental "rules," which lay out a scaffold for the vertebrate CNS without specific neuron-to-neuron recognition.

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Section: Discussionmentioning

confidence: 98%

Can Simple Rules Control Development of a Pioneer Vertebrate Neuronal Network Generating Behavior?

et al. 2014

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“…GFAP + glia are found surrounding the developing anterior commissure (Lent et al, 2005;Pires-Neto et al, 1998;Silver et al, 1993), although their origin and function have not been established. Future studies are required to determine whether Nf2-Yap signaling regulates the development of these putative anterior commissure guidepost cells and those involved in the formation of other axon tracts (Chedotal and Richards, 2010).…”

Section: Nf2 and Yap Regulate The Development Of Midline Guidepostsmentioning

confidence: 99%

The tumor suppressor Nf2 regulates corpus callosum development by inhibiting the transcriptional coactivator Yap

Lavado¹,

Ware²,

Paré³

et al. 2014

Journal of Cell Science

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The corpus callosum connects cerebral hemispheres and is the largest axon tract in the mammalian brain. Callosal malformations are among the most common congenital brain anomalies and are associated with a wide range of neuropsychological deficits. Crossing of the midline by callosal axons relies on a proper midline environment that harbors guidepost cells emitting guidance cues to instruct callosal axon navigation. Little is known about what controls the formation of the midline environment. We find that two components of the Hippo pathway, the tumor suppressor Nf2 (Merlin) and the transcriptional coactivator Yap (Yap1), regulate guidepost development and expression of the guidance cue Slit2 in mouse. During normal brain development, Nf2 suppresses Yap activity in neural progenitor cells to promote guidepost cell differentiation and prevent ectopic Slit2 expression. Loss of Nf2 causes malformation of midline guideposts and Slit2 upregulation, resulting in callosal agenesis. Slit2 heterozygosity and Yap deletion both restore callosal formation in Nf2 mutants. Furthermore, selectively elevating Yap activity in midline neural progenitors is sufficient to disrupt guidepost formation, upregulate Slit2 and prevent midline crossing. The Hippo pathway is known for its role in controlling organ growth and tumorigenesis. Our study identifies a novel role of this pathway in axon guidance. Moreover, by linking axon pathfinding and neural progenitor behaviors, our results provide an example of the intricate coordination between growth and wiring during brain development.

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“…Various ensembles of immature radial glia, other noncanonical glia and transient neurons predominate at these sites Lindwall et al 2007) (See Chédotal and Richards 2010). Glial cells at midline loci express both inhibitory and growth-promoting guidance factors, and serve to cordon axons into their proper tracts and to prevent them from straying (e.g., Plump et al 2002).…”

Section: Substrata In Vivomentioning

confidence: 99%

Cellular Strategies of Axonal Pathfinding

Raper

Mason

2010

Cold Spring Harbor Perspectives in Biology

157

130

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Axons follow highly stereotyped and reproducible trajectories to their targets. In this review we address the properties of the first pioneer neurons to grow in the developing nervous system and what has been learned over the past several decades about the extracellular and cell surface substrata on which axons grow. We then discuss the types of guidance cues and their receptors that influence axon extension, what determines where cues are expressed, and how axons respond to the cues they encounter in their environment.T his article provides an overview of how growth cones respond to the cellular substrata and molecular cues they encounter as they extend through the developing nervous system. It elaborates on the primer by Kolodkin and TessierLavigne (2010) and touches on many of the topics covered in greater detail in the articles that follow. The first sections describe how axons extend in a directed manner, the substrata on which they grow, interactions between pioneer and follower axons, and growth cone behaviors in emerging tracts and at decision points. The subsequent sections discuss examples of specific cues, their distributions, how their distributions are determined, and how growth cones integrate multiple cues during pathfinding. AXONS EXTEND IN VIVO IN A DIRECTED MANNERThe first person to visualize the growing tips of axons, Ramon y Cajal, recognized that axons for the most part grow very efficiently towards their ultimate targets. He was a strong advocate for axons finding their way in response to chemotactic cues:"If one admits that neuroblasts are endowed with chemotactic properties, then one might also imagine that they are capable of ameboid movements, initiated by factors secreted from epithelial, neural, or mesodermal elements. As a result, their processes may be oriented in the direction of chemical gradients, and thus guided to the secreting cells" (Ramon y Cajal 1892; trans. English, 1995).This surprisingly modern outlook emphasizing directed guidance was temporarily derailed by the views of Weiss during the 1920s and 1930s. He first argued that functional specificity did not arise as a consequence of specific axonal connections (Weiss 1936), and later argued that nonspecific mechanical guidance cues play a predominant role in guiding axons and organizing them into nerves and tracts

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Wiring the Brain: The Biology of Neuronal Guidance

Cited by 142 publications

References 151 publications

Can Simple Rules Control Development of a Pioneer Vertebrate Neuronal Network Generating Behavior?

Can Simple Rules Control Development of a Pioneer Vertebrate Neuronal Network Generating Behavior?

The tumor suppressor Nf2 regulates corpus callosum development by inhibiting the transcriptional coactivator Yap

Cellular Strategies of Axonal Pathfinding

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