To Stick or Not to Stick: The Multiple Roles of Cell Adhesion Molecules in Neural Circuit Assembly

Moreland, Trevor; Poulain, Fabienne E.

doi:10.3389/fnins.2022.889155

Cited by 23 publications

(20 citation statements)

References 205 publications

(222 reference statements)

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“…This suggests that these very different cell surface molecules may act not only through a shared set of cytoskeleton effectors but also through similar signaling effectors. The cell surface molecules identified in our screen are composed of very different structural motifs, including leucine-rich, immunoglobulin, YD or cadherin repeats 29, 30, 35, 65 . How these extracellular motifs or intracellular domains contribute to these shared effector modalities of actomyosin contractility and JNK signaling remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

A cell surface code mediates tissue-intrinsic defense against aberrant cells in epithelia

Fischer

Ernst

Frey

et al. 2023

Preprint

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Tissue-intrinsic error-correction mechanisms allow epithelial cells to detect aberrant neighboring cells and cause their removal from the tissue. The molecular mechanisms which grant cells the ability to compare their internal states is unknown. Here we demonstrate that comparison of cell identity, created by cell-fate-specifying transcription factors and patterning pathways, is conveyed through a specific set of cell surface molecules. We demonstrate thatDrosophilaimaginal discs express a range of cell surface molecules previously implicated in neuronal axon guidance processes, such as members of the Robo, Teneurin, Ephrin, Toll-like or atypical Cadherin families. Expression of these molecules is regulated by intrinsic fate-patterning pathways of the disc but also by aberrant expression of oncogenic RasV12. Importantly, mosaic clones deregulating individual cell surface molecules are sufficient to induce all hallmarks of interface surveillance, a tissue-intrinsic error-correction mechanism previously shown to be induced by cells with aberrant activation of fate-patterning pathways. Specifically, cells with deregulated expression of Robo2 and Robo3 induce actomyosin enrichment, bilateral JNK signaling and apoptosis at mosaic clone interfaces in imaginal discs. Moreover, deregulation of Robo2 levels, which is normally expressed in a complex endogenous pattern, induces these interface surveillance hallmarks in a Robo2-pattern-specific manner. Taken together, our work indicates that these cell surface molecules mediate cell fate recognition in epithelial tissues and thereby contribute to the maintenance of epithelial health by initiating detection and removal of aberrant cells during development and adult tissue homeostasis.

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Section: Discussionmentioning

confidence: 99%

A cell surface code mediates tissue-intrinsic defense against aberrant cells in epithelia

Fischer

Ernst

Frey

et al. 2023

Preprint

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“…While Notch activation is sufficient to instruct the L-DCN fate, hence preventing the formation of M-DCNs, it did not induce the retraction of an amplifying axon, nor reverse a M-DCN committed axon. Through the course of axon development, a plethora of signals modulates the intrinsic states of an immature neuron until it reaches its final state 28 . For DCNs in particular, JNK signalling acts downstream of Notch to impact DCN medulla innervation potential 1 and is additionally modulated by Wnt and FGF signalling 18 .…”

Section: Discussionmentioning

confidence: 99%

Probabilistic axon targeting dynamics lead to individualized brain wiring

Andriatsilavo

Dumoulin

Dutta

et al. 2022

Preprint

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Developmental variation in brain-wiring contributes to behavioural individuality1,2. However, how and when individualized wiring diagrams emerge and become stable during development remains largely unknown. Here, we explored axon targeting dynamics in individual brains using live-imaging of a developing Drosophila visual circuit and discovered that targeting choice is an algorithmic multi-step growth process with variable outcomes. Using optogenetics, we found that temporally restricted Notch lateral-inhibition defines a subset of neurons with a probabilistic potential to innervate distal targets. Next, axons from NotchOFF neurons amplify into long actin-rich multi-fibre structures necessary for distal growth. A subset of these NotchOFF neurons create distal targeting axons by stabilizing microtubule growth in one of their actin fibres. Amplified axons without tubulin-stabilized fibres retract, resulting in the stochastic selection of a different number of distal targeting axons in each brain. Pharmacological microtubule destabilization suffices to inhibit this targeting. We observed a similar axonal amplification-stabilization process in the developing chick spinal cord, suggesting a conserved mechanism. Finally, early microtubule patterns predict the adult brain- wiring of an individual in a target-independent manner prior to synapse formation3,4. Thus, we show that a temporal succession of genetically encoded stochastic processes explains the emergence of individual wiring variation.

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“…Once specified, CRH neurons undergo further differentiation, such as neuronal morphogenesis, synaptogenesis, epigenetic programming, and cell death, to establish a functional stress-responsive neural circuit. These later stages of neuronal differentiation are shaped by intercellular interactions mediated by membrane-localized cell-adhesion molecules ( Moreland and Poulain, 2022 ). The specific cell-adhesion molecules that mediate developmental signaling in CRH neurons, however, are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function

Brunal

Clark

et al. 2023

Front. Cell Dev. Biol.

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The corticotropin-releasing hormone (CRH)-expressing neurons in the hypothalamus are critical regulators of the neuroendocrine stress response pathway, known as the hypothalamic-pituitary-adrenal (HPA) axis. As developmental vulnerabilities of CRH neurons contribute to stress-associated neurological and behavioral dysfunctions, it is critical to identify the mechanisms underlying normal and abnormal CRH neuron development. Using zebrafish, we identified Down syndrome cell adhesion molecule like-1 (dscaml1) as an integral mediator of CRH neuron development and necessary for establishing normal stress axis function. In dscaml1 mutant animals, hypothalamic CRH neurons had higher crhb (the CRH homolog in zebrafish) expression, increased cell number, and reduced cell death compared to wild-type controls. Physiologically, dscaml1 mutant animals had higher baseline stress hormone (cortisol) levels and attenuated responses to acute stressors. Together, these findings identify dscaml1 as an essential factor for stress axis development and suggest that HPA axis dysregulation may contribute to the etiology of human DSCAML1-linked neuropsychiatric disorders.

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To Stick or Not to Stick: The Multiple Roles of Cell Adhesion Molecules in Neural Circuit Assembly

Cited by 23 publications

References 205 publications

A cell surface code mediates tissue-intrinsic defense against aberrant cells in epithelia

A cell surface code mediates tissue-intrinsic defense against aberrant cells in epithelia

Probabilistic axon targeting dynamics lead to individualized brain wiring

Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function

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