Sex-and Region-Dependent Expression of the Autism-Linked ADNP Correlates with Social- and Speech-Related Genes in the Canary Brain

J Mol Neurosci. 2020 Nov;70(11):1671-1683. doi: 10.1007/s12031-020-01700-x. Epub 2020 Sep 14.


The activity-dependent neuroprotective protein (ADNP) syndrome is an autistic-like disorder, instigated by mutations in ADNP. This syndrome is characterized by developmental delays, impairments in speech, motor function, abnormal hearing, and intellectual disabilities. In the Adnp-haploinsufficient mouse model, many of these impediments are evident, appearing in a sex-dependent manner. In zebra finch songbird (ZF; Taeniopygia guttata), an animal model used for song/language studies, ADNP mRNA most robust expression is observed in the cerebrum of young males, potentially corroborating with male ZF exclusive singing behavior and developed cerebral song system. Herein, we report a similar sex-dependent ADNP expression profile, with the highest expression in the cerebrum (qRT-PCR) in the brain of another songbird, the domesticated canary (Serinus canaria domestica). Additional analyses for the mRNA transcripts of the ADNP regulator, vasoactive intestinal peptide (VIP), sister gene ADNP2, and speech-related Forkhead box protein P2 (FoxP2) revealed multiple sex and brain region-dependent positive correlations between the genes (including ADNP). Parallel transcript expression patterns for FoxP2 and VIP were observed alongside specific FoxP2 increase in males compared with females as well as VIP/ADNP2 correlations. In spatial view, a sexually independent extensive form of expression was found for ADNP in the canary cerebrum (RNA in situ hybridization). The songbird cerebral mesopallium area stood out as a potentially high-expressing ADNP tissue, further strengthening the association of ADNP with sense integration and auditory memory formation, previously implicated in mouse and human.

Keywords: Activity-dependent neuroprotective protein (ADNP); Domesticated canary (Serinus canaria domestica); RNA in situ hybridization; Sexually dichotomous; The ADNP syndrome; Transcript expression.

MeSH terms

  • Animals
  • Autistic Disorder / genetics*
  • Avian Proteins / genetics
  • Avian Proteins / metabolism
  • Brain / metabolism*
  • Brain / physiology
  • Canaries / genetics*
  • Canaries / physiology
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Organ Specificity
  • Sex Factors
  • Vasoactive Intestinal Peptide / genetics
  • Vasoactive Intestinal Peptide / metabolism
  • Vocalization, Animal*


  • Avian Proteins
  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Vasoactive Intestinal Peptide