Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey

Angelman syndrome (AS) is a neurogenetic disorder caused by mutations or deletions in the maternally-inherited allele, leading to a loss of UBE3A protein expression in neurons. The paternally-inherited allele is epigenetically silenced in neurons during development by a noncoding transcript ( ). The...

Full description

Saved in:

Bibliographic Details
Published in:	Frontiers in neuroanatomy Vol. 18; p. 1410791
Main Authors:	Gonzalez Ramirez, Chavely, Salvador, Sarah G, Patel, Ridthi Kartik Rekha, Clark, Sarah, Miller, Noah W, James, Lucas M, Ringelberg, Nicholas W, Simon, Jeremy M, Bennett, Jeffrey, Amaral, David G, Burette, Alain C, Philpot, Benjamin D
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 30-05-2024
Subjects:	Angelman syndrome Dup15q syndrome E6-AP hippocampus Neuroscience rhesus macaque UBE3A-ATS Angelman syndrome rhesus macaque hippocampus Dup15q syndrome UBE3A-ATS E6-AP
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Angelman syndrome (AS) is a neurogenetic disorder caused by mutations or deletions in the maternally-inherited allele, leading to a loss of UBE3A protein expression in neurons. The paternally-inherited allele is epigenetically silenced in neurons during development by a noncoding transcript ( ). The absence of neuronal UBE3A results in severe neurological symptoms, including speech and language impairments, intellectual disability, and seizures. While no cure exists, therapies aiming to restore UBE3A function-either by gene addition or by targeting -are under development. Progress in developing these treatments relies heavily on inferences drawn from mouse studies about the function of UBE3A in the human brain. To aid translational efforts and to gain an understanding of UBE3A and biology with greater relevance to human neurodevelopmental contexts, we investigated UBE3A and expression in the developing brain of the rhesus macaque, a species that exhibits complex social behaviors, resembling aspects of human behavior to a greater degree than mice. Combining immunohistochemistry and hybridization, we mapped UBE3A and regional and cellular expression in normal prenatal, neonatal, and adolescent rhesus macaque brains. We show that key hallmarks of UBE3A biology, well-known in rodents, are also present in macaques, and suggest paternal silencing in neurons-but not glial cells-in the macaque brain, with onset between gestational day 48 and 100. These findings support proposals that early-life, perhaps even prenatal, intervention is optimal for overcoming the maternal allele loss of linked to AS.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Greta Pintacuda, Broad Institute, United States Reviewed by: Simon Trent, Keele University, United Kingdom These authors have contributed equally to this work and share first authorship Edited by: Jean-Jacques Soghomonian, Boston University, United States
ISSN:	1662-5129 1662-5129
DOI:	10.3389/fnana.2024.1410791