<scp>Jag2b‐Notch3</scp>/1b‐mediated neuron‐to‐glia crosstalk controls retinal gliogenesis

Jin, Mengmeng; Zhang, Hui; Xu, Baijie; Li, Yanan; Qin, Huiwen; Yu, Song; He, Jie

doi:10.15252/embr.202254922

Cited by 3 publications

(1 citation statement)

References 53 publications

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“…Total RNA was isolated using the lysis buffer. cDNA synthesis and amplification were performed using the protocol in our lab ( Jin et al, 2022 ) by adding RT mix (200 U Superscript II reverse transcriptase [18064-014; Invitrogen], 1× First-strand buffer [18064-014; Invitrogen], 5 mM DTT [18064-014; Invitrogen], 20 U Recombinant RNase inhibitor [2313A; Clontech], 6 mM MgCl 2 [M8266; Sigma-Aldrich], 1 µM TSO [ Picelli et al, 2013 ], and 8% PEG8000 [P1458; Sigma-Aldrich]).…”

Section: Methodsmentioning

confidence: 99%

Homophilic interaction of cell adhesion molecule 3 coordinates retina neuroepithelial cell proliferation

Jin

et al. 2023

Journal of Cell Biology

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Correct cell number generation is central to tissue development. However, in vivo roles of coordinated proliferation of individual neural progenitors in regulating cell numbers of developing neural tissues and the underlying molecular mechanism remain mostly elusive. Here, we showed that wild-type (WT) donor retinal progenitor cells (RPCs) generated significantly expanded clones in host retinae with G1-lengthening by p15 (cdkn2a/b) overexpression (p15+) in zebrafish. Further analysis showed that cell adhesion molecule 3 (cadm3) was reduced in p15+ host retinae, and overexpression of either full-length or ectodomains of Cadm3 in p15+ host retinae markedly suppressed the clonal expansion of WT donor RPCs. Notably, WT donor RPCs in retinae with cadm3 disruption recapitulated expanded clones that were found in p15+ retinae. More strikingly, overexpression of Cadm3 without extracellular ig1 domain in RPCs resulted in expanded clones and increased retinal total cell number. Thus, homophilic interaction of Cadm3 provides an intercellular mechanism underlying coordinated cell proliferation to ensure cell number homeostasis of the developing neuroepithelia.

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Section: Methodsmentioning

confidence: 99%

Homophilic interaction of cell adhesion molecule 3 coordinates retina neuroepithelial cell proliferation

Jin

et al. 2023

Journal of Cell Biology

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Jag2b‐Notch3/1b‐mediated neuron‐to‐glia crosstalk controls retinal gliogenesis

Jin

Zhang

et al. 2022

EMBO Reports

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In the developing central nervous systems (CNS), neural progenitor cells generate neurons and glia in sequential order. However, the influence of neurons on glia generation remains elusive. Here, we report that photoreceptor cell-derived Jag2b is required for Notchdependent M€ uller glia (MG) generation in the developing zebrafish retina. In jab2b À/À mutants, differentiating MGs are re-specified into lineage-related bipolar neuron fate at the expense of mature MG. Single-cell transcriptome analysis and knock-in animals reveal that jab2b is specifically expressed in crx + -photoreceptor cells during MG generation. Crx promoter-driven jag2b, but not other Notch ligands, is sufficient to rescue the loss of MGs observed in jag2b À/À mutants. Furthermore, we observe a severe and moderate decrease in the number of MGs in notch3 À/À and notch1b À/À mutants, respectively, and the activation of Notch3 or Notch1b rescues the MG loss in jag2b À/À mutants. Together, our findings reveal that the interaction of Jag2b and Notch3/Notch1b mediates the crosstalk between neurons and glial cells to ensure the irreversible differentiation of MG, providing novel mechanistic insights into the temporal specification of glial cell fate in a developing vertebrate CNS structure.

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An Orthologics Study of the Notch Signaling Pathway

Stein

2024

Genes

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The Notch signaling pathway plays a major role in embryological development and in the ongoing life processes of many animals. Its role is to provide cell-to-cell communication in which a Sender cell, bearing membrane-embedded ligands, instructs a Receiver cell, bearing membrane-embedded receptors, to adopt one of two available fates. Elucidating the evolution of this pathway is the topic of this paper, which uses an orthologs approach, providing a comprehensive basis for the study. Using BLAST searches, orthologs were identified for all the 49 components of the Notch signaling pathway. The historical time course of integration of these proteins, as the animals evolved, was elucidated. Insofar as cell-to-cell communication is of relevance only in multicellular animals, it is not surprising that the Notch system became functional only with the evolutionary appearance of Metazoa, the first multicellular animals. Porifera contributed a quarter of the Notch pathway proteins, the Cnidaria brought the total to one-half, but the system reached completion only when humans appeared. A literature search elucidated the roles of the Notch system’s components in modern descendants of the ortholog-contributing ancestors. A single protein, the protein tyrosine kinase (PTK) of the protozoan Ministeria vibrans, was identified as a possible pre-Metazoan ancestor of all three of the Notch pathway proteins, DLL, JAG, and NOTCH. A scenario for the evolution of the Notch signaling pathway is presented and described as the co-option of its components, clade by clade, in a repurposing of genes already present in ancestral unicellular organisms.

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Jag2b‐Notch3/1b‐mediated neuron‐to‐glia crosstalk controls retinal gliogenesis

Cited by 3 publications

References 53 publications

Homophilic interaction of cell adhesion molecule 3 coordinates retina neuroepithelial cell proliferation

Homophilic interaction of cell adhesion molecule 3 coordinates retina neuroepithelial cell proliferation

Jag2b‐Notch3/1b‐mediated neuron‐to‐glia crosstalk controls retinal gliogenesis

An Orthologics Study of the Notch Signaling Pathway

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