Subclass‐specific expression patterns of MET receptor tyrosine kinase during development in medial prefrontal and visual cortices

• Published in: Journal of comparative neurology (1911) Vol. 531; no. 1; pp. 132 - 148
• Main Authors: Lanjewar, Alexandra L., Jagetia, Sonum, Khan, Zuhayr M., Eagleson, Kathie L., Levitt, Pat
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2023; John Wiley and Sons Inc
• Subjects: Animals; c-Met protein; Cognitive ability; Confocal microscopy; Cortex (temporal); cortico‐cortical; Critical period; Embryogenesis; Fear - physiology; Female; Green fluorescent protein; Immunofluorescence; MET receptor tyrosine kinase; Mice; Mice, Transgenic; molecular heterogeneity; Nervous system; neuronal subclasses; Neurons; Neurons - metabolism; Ocular dominance; Prefrontal cortex; Prefrontal Cortex - metabolism; Pregnancy; projection neurons; Protein-tyrosine kinase receptors; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins c-met - metabolism; subcerebral; Synaptogenesis; Transgenic mice; Visual cortex; Visual Cortex - metabolism; Visual pathways; Visual plasticity; cortico-cortical; neuronal subclasses; projection neurons; molecular heterogeneity; MET receptor tyrosine kinase; subcerebral
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.25418

Met encodes a receptor tyrosine kinase (MET) that is expressed during development and regulates cortical synapse maturation. Conditional deletion of Met in the nervous system during embryonic development leads to deficits in adult contextual fear learning, a medial prefrontal cortex (mPFC)‐dependent cognitive task. MET also regulates the timing of critical period plasticity for ocular dominance in primary visual cortex (V1). However, the underlying circuitry responsible remains unknown. Therefore, this study determines the broad expression patterns of MET throughout postnatal development in mPFC and V1 projection neurons (PNs), providing insight into similarities and differences in the neuronal subtypes and temporal patterns of MET expression between cortical areas. Using a transgenic mouse line that expresses green fluorescent protein (GFP) in Met+ neurons, immunofluorescence and confocal microscopy were performed to visualize MET‐GFP+ cell bodies and PN subclass‐specific protein markers. Analyses reveal that the MET expression is highly enriched in infragranular layers of mPFC, but in supragranular layers of V1. Interestingly, temporal regulation of the percentage of MET+ neurons across development not only differs between cortical regions but also is distinct between lamina within a cortical region. Further, MET is expressed predominantly in the subcerebral PN subclass in mPFC, but the intratelencephalic PN subclass in V1. The data suggest that MET signaling influences the development of distinct circuits in mPFC and V1 that underlie subcerebral and intracortical functional deficits following Met deletion, respectively. Percentage of MET‐expressing neurons in medial prefrontal and primary visual (V1) cortices varies between layer and age in mice. The predominant subclass of MET+ projection neurons in mPFC is subcortical, including corticothalamic, whereas it is intratelencephalic in V1, demonstrating stark heterogeneity between cortical regions.