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Retinoic acid induced-1 (Rai1) regulates craniofacial and brain development in Xenopus.
Mech Dev 2014; 133:91-104MD

Abstract

Retinoic acid induced-1 (RAI1) is an important yet understudied histone code reader that when mutated in humans results in Smith-Magenis syndrome (SMS), a neurobehavioral disorder accompanied by signature craniofacial abnormalities. Despite previous studies in mouse and human cell models, very little is known about the function of RAI1 during embryonic development. In the present study, we have turned to the model vertebrates Xenopus laevis and Xenopus tropicalis to better understand the developmental roles of Rai1. First we demonstrate that the Rai1 protein sequence is conserved in frogs, especially in known functional domains. By in situ hybridization we revealed expression of rai1 in the developing craniofacial tissues and the nervous system. Knockdown of Rai1 using antisense morpholinos resulted in defects in the developing brain and face. In particular, Rai1 morphants display midface hypoplasia and malformed mouth shape analogous to defects in humans with SMS. These craniofacial defects were accompanied with aberrant neural crest migration and reduction in the size of facial cartilage elements. Rai1 morphants also had defects in axon patterns and decreased forebrain ventricle size. Such brain defects correlated with a decrease in the neurotrophic factor, bdnf, and increased forebrain apoptosis. Our results emphasize a critical role of Rai1 for normal neural and craniofacial development, and further the current understanding of potential mechanisms that cause SMS.

Authors+Show Affiliations

Center of the Study of Biological Complexity, Virginia Commonwealth University, Richmond, VA 23284, USA.Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, USA.Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, MS NAB2015, Houston, TX 77030, USA.Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, USA. Electronic address: ajdickinson@vcu.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24878353

Citation

Tahir, Raiha, et al. "Retinoic Acid Induced-1 (Rai1) Regulates Craniofacial and Brain Development in Xenopus." Mechanisms of Development, vol. 133, 2014, pp. 91-104.
Tahir R, Kennedy A, Elsea SH, et al. Retinoic acid induced-1 (Rai1) regulates craniofacial and brain development in Xenopus. Mech Dev. 2014;133:91-104.
Tahir, R., Kennedy, A., Elsea, S. H., & Dickinson, A. J. (2014). Retinoic acid induced-1 (Rai1) regulates craniofacial and brain development in Xenopus. Mechanisms of Development, 133, pp. 91-104. doi:10.1016/j.mod.2014.05.004.
Tahir R, et al. Retinoic Acid Induced-1 (Rai1) Regulates Craniofacial and Brain Development in Xenopus. Mech Dev. 2014;133:91-104. PubMed PMID: 24878353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Retinoic acid induced-1 (Rai1) regulates craniofacial and brain development in Xenopus. AU - Tahir,Raiha, AU - Kennedy,Allyson, AU - Elsea,Sarah H, AU - Dickinson,Amanda J, Y1 - 2014/05/27/ PY - 2014/03/04/received PY - 2014/05/16/revised PY - 2014/05/19/accepted PY - 2014/6/1/entrez PY - 2014/6/1/pubmed PY - 2015/6/24/medline KW - Brain KW - Craniofacial KW - Rai1 KW - Xenopus SP - 91 EP - 104 JF - Mechanisms of development JO - Mech. Dev. VL - 133 N2 - Retinoic acid induced-1 (RAI1) is an important yet understudied histone code reader that when mutated in humans results in Smith-Magenis syndrome (SMS), a neurobehavioral disorder accompanied by signature craniofacial abnormalities. Despite previous studies in mouse and human cell models, very little is known about the function of RAI1 during embryonic development. In the present study, we have turned to the model vertebrates Xenopus laevis and Xenopus tropicalis to better understand the developmental roles of Rai1. First we demonstrate that the Rai1 protein sequence is conserved in frogs, especially in known functional domains. By in situ hybridization we revealed expression of rai1 in the developing craniofacial tissues and the nervous system. Knockdown of Rai1 using antisense morpholinos resulted in defects in the developing brain and face. In particular, Rai1 morphants display midface hypoplasia and malformed mouth shape analogous to defects in humans with SMS. These craniofacial defects were accompanied with aberrant neural crest migration and reduction in the size of facial cartilage elements. Rai1 morphants also had defects in axon patterns and decreased forebrain ventricle size. Such brain defects correlated with a decrease in the neurotrophic factor, bdnf, and increased forebrain apoptosis. Our results emphasize a critical role of Rai1 for normal neural and craniofacial development, and further the current understanding of potential mechanisms that cause SMS. SN - 1872-6356 UR - https://www.unboundmedicine.com/medline/citation/24878353/Retinoic_acid_induced_1__Rai1__regulates_craniofacial_and_brain_development_in_Xenopus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0925-4773(14)00028-8 DB - PRIME DP - Unbound Medicine ER -