Synaptic recognition molecules in development and disease

Curr Top Dev Biol. 2021;142:319-370. doi: 10.1016/bs.ctdb.2020.12.009. Epub 2021 Feb 12.

Abstract

Synaptic connectivity patterns underlie brain functions. How recognition molecules control where and when neurons form synapses with each other, therefore, is a fundamental question of cellular neuroscience. This chapter delineates adhesion and signaling complexes as well as secreted factors that contribute to synaptic partner recognition in the vertebrate brain. The sections follow a developmental perspective and discuss how recognition molecules (1) guide initial synaptic wiring, (2) provide for the rejection of incorrect partner choices, (3) contribute to synapse specification, and (4) support the removal of inappropriate synapses once formed. These processes involve a rich repertoire of molecular players and key protein families are described, notably the Cadherin and immunoglobulin superfamilies, Semaphorins/Plexins, Leucine-rich repeat containing proteins, and Neurexins and their binding partners. Molecular themes that diversify these recognition systems are defined and highlighted throughout the text, including the neuron-type specific expression and combinatorial action of recognition factors, alternative splicing, and post-translational modifications. Methodological innovations advancing the field such as proteomic approaches and single cell expression studies are additionally described. Further, the chapter highlights the importance of choosing an appropriate brain region to analyze synaptic recognition factors and the advantages offered by laminated structures like the hippocampus or retina. In a concluding section, the profound disease relevance of aberrant synaptic recognition for neurodevelopmental and psychiatric disorders is discussed. Based on the current progress, an outlook is presented on research goals that can further advance insights into how recognition molecules provide for the astounding precision and diversity of synaptic connections.

Keywords: Cadherins; Immunoglobulin proteins; Leucine-rich repeat proteins; Neuronal connectivity; Semaphorins; Synapse; Synapse elimination; Synapse specification; Synaptic adhesion; Synaptic recognition.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Brain / physiology*
  • Humans
  • Proteomics
  • Synapses*