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Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development

Sonic hedgehog (Shh) signaling regulates multiple morphogenetic processes during embryonic neurogenesis and craniofacial skeletal development. Gpr161 is a known negative regulator of Shh signaling. Nullizygous Gpr161 mice are embryonic lethal, presenting with structural defects involving the neural...

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Autores principales: Kim, Sung-Eun, Robles-Lopez, Karla, Cao, Xuanye, Liu, Kristyn, Chothani, Pooja J., Bhavani, Nikitha, Rahman, Lauren, Mukhopadhyay, Saikat, Wlodarczyk, Bogdan J., Finnell, Richard H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650154/
https://www.ncbi.nlm.nih.gov/pubmed/34887903
http://dx.doi.org/10.3389/fgene.2021.761418
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author Kim, Sung-Eun
Robles-Lopez, Karla
Cao, Xuanye
Liu, Kristyn
Chothani, Pooja J.
Bhavani, Nikitha
Rahman, Lauren
Mukhopadhyay, Saikat
Wlodarczyk, Bogdan J.
Finnell, Richard H.
author_facet Kim, Sung-Eun
Robles-Lopez, Karla
Cao, Xuanye
Liu, Kristyn
Chothani, Pooja J.
Bhavani, Nikitha
Rahman, Lauren
Mukhopadhyay, Saikat
Wlodarczyk, Bogdan J.
Finnell, Richard H.
author_sort Kim, Sung-Eun
collection PubMed
description Sonic hedgehog (Shh) signaling regulates multiple morphogenetic processes during embryonic neurogenesis and craniofacial skeletal development. Gpr161 is a known negative regulator of Shh signaling. Nullizygous Gpr161 mice are embryonic lethal, presenting with structural defects involving the neural tube and the craniofacies. However, the lineage specific role of Gpr161 in later embryonic development has not been thoroughly investigated. We studied the Wnt1-Cre lineage specific role of Gpr161 during mouse embryonic development. We observed three major gross morphological phenotypes in Gpr161 cKO (Gpr161 f/f; Wnt1-Cre) fetuses; protrusive tectum defect, encephalocele, and craniofacial skeletal defect. The overall midbrain tissues were expanded and cell proliferation in ventricular zones of midbrain was increased in Gpr161 cKO fetuses, suggesting that protrusive tectal defects in Gpr161 cKO are secondary to the increased proliferation of midbrain neural progenitor cells. Shh signaling activity as well as upstream Wnt signaling activity were increased in midbrain tissues of Gpr161 cKO fetuses. RNA sequencing further suggested that genes in the Shh, Wnt, Fgf and Notch signaling pathways were differentially regulated in the midbrain of Gpr161 cKO fetuses. Finally, we determined that cranial neural crest derived craniofacial bone formation was significantly inhibited in Gpr161 cKO fetuses, which partly explains the development of encephalocele. Our results suggest that Gpr161 plays a distinct role in midbrain development and in the formation of the craniofacial skeleton during mouse embryogenesis.
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spelling pubmed-86501542021-12-08 Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development Kim, Sung-Eun Robles-Lopez, Karla Cao, Xuanye Liu, Kristyn Chothani, Pooja J. Bhavani, Nikitha Rahman, Lauren Mukhopadhyay, Saikat Wlodarczyk, Bogdan J. Finnell, Richard H. Front Genet Genetics Sonic hedgehog (Shh) signaling regulates multiple morphogenetic processes during embryonic neurogenesis and craniofacial skeletal development. Gpr161 is a known negative regulator of Shh signaling. Nullizygous Gpr161 mice are embryonic lethal, presenting with structural defects involving the neural tube and the craniofacies. However, the lineage specific role of Gpr161 in later embryonic development has not been thoroughly investigated. We studied the Wnt1-Cre lineage specific role of Gpr161 during mouse embryonic development. We observed three major gross morphological phenotypes in Gpr161 cKO (Gpr161 f/f; Wnt1-Cre) fetuses; protrusive tectum defect, encephalocele, and craniofacial skeletal defect. The overall midbrain tissues were expanded and cell proliferation in ventricular zones of midbrain was increased in Gpr161 cKO fetuses, suggesting that protrusive tectal defects in Gpr161 cKO are secondary to the increased proliferation of midbrain neural progenitor cells. Shh signaling activity as well as upstream Wnt signaling activity were increased in midbrain tissues of Gpr161 cKO fetuses. RNA sequencing further suggested that genes in the Shh, Wnt, Fgf and Notch signaling pathways were differentially regulated in the midbrain of Gpr161 cKO fetuses. Finally, we determined that cranial neural crest derived craniofacial bone formation was significantly inhibited in Gpr161 cKO fetuses, which partly explains the development of encephalocele. Our results suggest that Gpr161 plays a distinct role in midbrain development and in the formation of the craniofacial skeleton during mouse embryogenesis. Frontiers Media S.A. 2021-11-23 /pmc/articles/PMC8650154/ /pubmed/34887903 http://dx.doi.org/10.3389/fgene.2021.761418 Text en Copyright © 2021 Kim, Robles-Lopez, Cao, Liu, Chothani, Bhavani, Rahman, Mukhopadhyay, Wlodarczyk and Finnell. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Kim, Sung-Eun
Robles-Lopez, Karla
Cao, Xuanye
Liu, Kristyn
Chothani, Pooja J.
Bhavani, Nikitha
Rahman, Lauren
Mukhopadhyay, Saikat
Wlodarczyk, Bogdan J.
Finnell, Richard H.
Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development
title Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development
title_full Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development
title_fullStr Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development
title_full_unstemmed Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development
title_short Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development
title_sort wnt1 lineage specific deletion of gpr161 results in embryonic midbrain malformation and failure of craniofacial skeletal development
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650154/
https://www.ncbi.nlm.nih.gov/pubmed/34887903
http://dx.doi.org/10.3389/fgene.2021.761418
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