A negative regulator of synaptic development: MDGA and its links to neurodevelopmental disorders

  • Rui Wang
  • Jia-Xian Dong
  • Lu Wang
  • Xin-Yan Dong
  • Eitan Anenberg
  • Pei-Fang Jiang
  • Ling-Hui Zeng
  • Yi-Cheng XieEmail author
Review Article



Formation of protein complexes across synapses is a critical process in neurodevelopment, having direct implications on brain function and animal behavior. Here, we present the understanding, importance, and potential impact of a newly found regulator of such a key interaction.

Data sources

A systematic search of the literature was conducted on PubMed (Medline), Embase, and Central-Cochrane Database.


Membrane-associated mucin domain-containing glycosylphosphatidylinositol anchor proteins (MDGAs) were recently discovered to regulate synaptic development and transmission via suppression of neurexins–neuroligins trans-synaptic complex formation. MDGAs also regulate axonal migration and outgrowth. In the context of their physiological role, we begin to consider the potential links to the etiology of certain neurodevelopmental disorders. We present the gene expression and protein structure of MDGAs and discuss recent progress in our understanding of the neurobiological role of MDGAs to explore its potential as a therapeutic target.


MDGAs play a key role in neuron migration, axon guidance and synapse development, as well as in regulating brain excitation and inhibition balance.


Adhesion molecule E/I balance Neurodevelopmental disorders Synapse 


Author contributions

Rui Wang and Yi-Cheng Xie drafted the manuscript. All the others participated in the writing and discussion, and approved the final version of the manuscript.


This work was supported by a grant from Zhejiang Province Public Welfare Technology Application Research Project (No. LQ19C090007), the start funds of the Children’s Hospital Zhejiang University School of Medicine and ERA-NET SynPathy from Neuron Network of European Funding for Neuroscience Research.

Compliance with ethical standards

Ethical approval

No ethnical approval is required for this review article.

Conflict of interest

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.


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Copyright information

© Children's Hospital, Zhejiang University School of Medicine 2019

Authors and Affiliations

  1. 1.Children’s HospitalZhejiang University School of MedicineHangzhouChina
  2. 2.Department of Clinical MedicineZhejiang University City CollegeHangzhouChina

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