Impaired neurodevelopmental pathways in autism spectrum disorder: A review of signaling mechanisms and crosstalk

Santosh Kumar, Kurt Reynolds, Yu Ji, Ran Gu, Sunil Rai, Chengji Zhou

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations


Background: The development of an autistic brain is a highly complex process as evident from the involvement of various genetic and non-genetic factors in the etiology of the autism spectrum disorder (ASD). Despite being a multifactorial neurodevelopmental disorder, autistic patients display a few key characteristics, such as the impaired social interactions and elevated repetitive behaviors, suggesting the perturbation of specific neuronal circuits resulted from abnormal signaling pathways during brain development in ASD. A comprehensive review for autistic signaling mechanisms and interactions may provide a better understanding of ASD etiology and treatment. Main body: Recent studies on genetic models and ASD patients with several different mutated genes revealed the dysregulation of several key signaling pathways, such as WNT, BMP, SHH, and retinoic acid (RA) signaling. Although no direct evidence of dysfunctional FGF or TGF-β signaling in ASD has been reported so far, a few examples of indirect evidence can be found. This review article summarizes how various genetic and non-genetic factors which have been reported contributing to ASD interact with WNT, BMP/TGF-β, SHH, FGF, and RA signaling pathways. The autism-associated gene ubiquitin-protein ligase E3A (UBE3A) has been reported to influence WNT, BMP, and RA signaling pathways, suggesting crosstalk between various signaling pathways during autistic brain development. Finally, the article comments on what further studies could be performed to gain deeper insights into the understanding of perturbed signaling pathways in the etiology of ASD. Conclusion: The understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods.

Original languageEnglish (US)
Article number10
JournalJournal of Neurodevelopmental Disorders
Issue number1
StatePublished - Jun 15 2019


  • Autism spectrum disorder
  • BMP/TGF-β
  • FGF
  • Neurodevelopmental disorders
  • Retinoic acid (RA)
  • SHH
  • Signaling crosstalk
  • WNT

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cognitive Neuroscience


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