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Related Experiment Video

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Single-cell Profiling of Developing and Mature Retinal Neurons
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Comparative Single-Cell Transcriptome Analysis of c-Met Receptor Expressing and Non-Expressing Projection Neurons in

Ramin Ali Marandi Ghoddousi1,2, Pat Levitt3,4, Zia Rady5

  • 1Developmental Neuroscience and Neurogenetics Program, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA, rghoddousi@g.ucla.edu.

Developmental Neuroscience
|September 25, 2025
PubMed
Summary

MET receptor tyrosine kinase (MET) expression in mouse cortical projection neurons correlates with a less mature state. This suggests MET signaling contributes to the asynchronous development of cortical circuits during early synapse formation.

Keywords:
Developing neocortexMETNeocortical subclass heterogeneitySingle molecule fluorescent in situ hybridizationSingle-cell RNA sequencing

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Developmental Biology

Background:

  • Cortical projection neurons display transcriptomic heterogeneity linked to position and targets.
  • This heterogeneity arises partly from differing maturation states.
  • The MET receptor tyrosine kinase (MET) is expressed in a subpopulation, offering a model for studying developmental heterogeneity.

Purpose of the Study:

  • To investigate transcriptomic differences between Met+ and Met- projection neurons.
  • To explore the role of MET signaling in cortical circuit development and maturation.

Main Methods:

  • Single-cell RNA sequencing and smFISH were employed.
  • Analysis focused on mouse visual and frontal cortices during early synapse formation.

Main Results:

  • MET was enriched in specific projection neuron subclasses, with astrocytes identified as the primary source of its ligand, Hgf.
  • Graded gene expression differences, not unique genes, distinguished Met+ and Met- populations.
  • Met+ neurons showed gene expression patterns indicating less mature synapses and spines compared to Met- neurons.

Conclusions:

  • Met+ projection neurons are in a less mature state than Met- neurons within the same subclass.
  • MET signaling appears to contribute to the asynchronous maturation of developing cortical circuits.