ANKRD11 associated with intellectual disability and autism regulates dendrite differentiation via the BDNF/TrkB signaling pathway

Minhan Ka, Woo Yang Kim

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Haploinsufficiency of ANKRD11 due to deletion or truncation mutations causes KBG syndrome, a rare genetic disorder characterized by intellectual disability, autism spectrum disorder, and craniofacial abnormalities. However, little is known about the neurobiological role of ANKRD11 during brain development. Here we show that ANKRD11 regulates pyramidal neuron migration and dendritic differentiation in the developing mouse cerebral cortex. Using an in utero manipulation approach, we found that Ankrd11 knockdown delayed radial migration of cortical neurons. ANKRD11-deficient neurons displayed markedly reduced dendrite growth and branching as well as abnormal dendritic spine morphology. Ankrd11 knockdown suppressed acetylation of epigenetic molecules such as p53 and Histone H3. Furthermore, the mRNA levels of Trkb, Bdnf, and neurite growth-related genes were downregulated in ANKRD11-deficient cortical neurons. The Trkb promoter region was largely devoid of acetylated Histone H3 and p53, and was instead occupied with MeCP2 and DNMT1. Overexpression of TrkB rescued abnormal dendrite growth in these cells. Our findings demonstrate a novel role for ANKRD11 in neuron differentiation during brain development and suggest an epigenetic modification as a potential key molecular feature underlying KBG syndrome.

Original languageEnglish (US)
Pages (from-to)138-152
Number of pages15
JournalNeurobiology of Disease
Volume111
DOIs
StatePublished - Mar 2018

Fingerprint

Brain-Derived Neurotrophic Factor
Autistic Disorder
Dendrites
Intellectual Disability
Neurons
Epigenomics
Histones
Growth
Craniofacial Abnormalities
Haploinsufficiency
Dendritic Spines
Inborn Genetic Diseases
Pyramidal Cells
Brain
Neurites
Acetylation
Genetic Promoter Regions
Cerebral Cortex
Down-Regulation
Messenger RNA

Keywords

  • ANKRD11
  • Arborization
  • Autism
  • BDNF
  • Dendrite
  • Dendritic spine
  • Histone acetylation
  • Intellectual disability
  • TrkB

ASJC Scopus subject areas

  • Neurology

Cite this

ANKRD11 associated with intellectual disability and autism regulates dendrite differentiation via the BDNF/TrkB signaling pathway. / Ka, Minhan; Kim, Woo Yang.

In: Neurobiology of Disease, Vol. 111, 03.2018, p. 138-152.

Research output: Contribution to journalArticle

@article{2c7903e45e104bef81c639dc3bc84264,
title = "ANKRD11 associated with intellectual disability and autism regulates dendrite differentiation via the BDNF/TrkB signaling pathway",
abstract = "Haploinsufficiency of ANKRD11 due to deletion or truncation mutations causes KBG syndrome, a rare genetic disorder characterized by intellectual disability, autism spectrum disorder, and craniofacial abnormalities. However, little is known about the neurobiological role of ANKRD11 during brain development. Here we show that ANKRD11 regulates pyramidal neuron migration and dendritic differentiation in the developing mouse cerebral cortex. Using an in utero manipulation approach, we found that Ankrd11 knockdown delayed radial migration of cortical neurons. ANKRD11-deficient neurons displayed markedly reduced dendrite growth and branching as well as abnormal dendritic spine morphology. Ankrd11 knockdown suppressed acetylation of epigenetic molecules such as p53 and Histone H3. Furthermore, the mRNA levels of Trkb, Bdnf, and neurite growth-related genes were downregulated in ANKRD11-deficient cortical neurons. The Trkb promoter region was largely devoid of acetylated Histone H3 and p53, and was instead occupied with MeCP2 and DNMT1. Overexpression of TrkB rescued abnormal dendrite growth in these cells. Our findings demonstrate a novel role for ANKRD11 in neuron differentiation during brain development and suggest an epigenetic modification as a potential key molecular feature underlying KBG syndrome.",
keywords = "ANKRD11, Arborization, Autism, BDNF, Dendrite, Dendritic spine, Histone acetylation, Intellectual disability, TrkB",
author = "Minhan Ka and Kim, {Woo Yang}",
year = "2018",
month = "3",
doi = "10.1016/j.nbd.2017.12.008",
language = "English (US)",
volume = "111",
pages = "138--152",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - ANKRD11 associated with intellectual disability and autism regulates dendrite differentiation via the BDNF/TrkB signaling pathway

AU - Ka, Minhan

AU - Kim, Woo Yang

PY - 2018/3

Y1 - 2018/3

N2 - Haploinsufficiency of ANKRD11 due to deletion or truncation mutations causes KBG syndrome, a rare genetic disorder characterized by intellectual disability, autism spectrum disorder, and craniofacial abnormalities. However, little is known about the neurobiological role of ANKRD11 during brain development. Here we show that ANKRD11 regulates pyramidal neuron migration and dendritic differentiation in the developing mouse cerebral cortex. Using an in utero manipulation approach, we found that Ankrd11 knockdown delayed radial migration of cortical neurons. ANKRD11-deficient neurons displayed markedly reduced dendrite growth and branching as well as abnormal dendritic spine morphology. Ankrd11 knockdown suppressed acetylation of epigenetic molecules such as p53 and Histone H3. Furthermore, the mRNA levels of Trkb, Bdnf, and neurite growth-related genes were downregulated in ANKRD11-deficient cortical neurons. The Trkb promoter region was largely devoid of acetylated Histone H3 and p53, and was instead occupied with MeCP2 and DNMT1. Overexpression of TrkB rescued abnormal dendrite growth in these cells. Our findings demonstrate a novel role for ANKRD11 in neuron differentiation during brain development and suggest an epigenetic modification as a potential key molecular feature underlying KBG syndrome.

AB - Haploinsufficiency of ANKRD11 due to deletion or truncation mutations causes KBG syndrome, a rare genetic disorder characterized by intellectual disability, autism spectrum disorder, and craniofacial abnormalities. However, little is known about the neurobiological role of ANKRD11 during brain development. Here we show that ANKRD11 regulates pyramidal neuron migration and dendritic differentiation in the developing mouse cerebral cortex. Using an in utero manipulation approach, we found that Ankrd11 knockdown delayed radial migration of cortical neurons. ANKRD11-deficient neurons displayed markedly reduced dendrite growth and branching as well as abnormal dendritic spine morphology. Ankrd11 knockdown suppressed acetylation of epigenetic molecules such as p53 and Histone H3. Furthermore, the mRNA levels of Trkb, Bdnf, and neurite growth-related genes were downregulated in ANKRD11-deficient cortical neurons. The Trkb promoter region was largely devoid of acetylated Histone H3 and p53, and was instead occupied with MeCP2 and DNMT1. Overexpression of TrkB rescued abnormal dendrite growth in these cells. Our findings demonstrate a novel role for ANKRD11 in neuron differentiation during brain development and suggest an epigenetic modification as a potential key molecular feature underlying KBG syndrome.

KW - ANKRD11

KW - Arborization

KW - Autism

KW - BDNF

KW - Dendrite

KW - Dendritic spine

KW - Histone acetylation

KW - Intellectual disability

KW - TrkB

UR - http://www.scopus.com/inward/record.url?scp=85039808081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039808081&partnerID=8YFLogxK

U2 - 10.1016/j.nbd.2017.12.008

DO - 10.1016/j.nbd.2017.12.008

M3 - Article

C2 - 29274743

AN - SCOPUS:85039808081

VL - 111

SP - 138

EP - 152

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

ER -