Intra-amniotic transient transduction of the periderm with a viral vector encoding TGFβ3 prevents cleft palate in Tgfβ3(-/-) mouse embryos

Molecular Therapy : the Journal of the American Society of Gene Therapy
Chadwick WuHyun-Duck Nah

Abstract

Cleft palate is a developmental defect resulting from the failure of embryonic palatal shelves to fuse with each other at a critical time. Immediately before and during palatal fusion (E13-E15 in mice), transforming growth factor β3 (TGFβ3) is expressed in the palatal shelf medial edge epithelium (MEE) and plays a pivotal role in palatal fusion. Using Tgfβ3(-/-) mice, which display complete penetrance of the cleft palate phenotype, we tested the hypothesis that intra-amniotic gene transfer could be used to prevent cleft palate formation by restoring palatal midline epithelial function. An adenoviral vector encoding Tgfβ3 was microinjected into the amniotic sacs of mouse embryos at successive developmental stages. Transduced Tgfβ3(-/-) fetuses showed efficient recovery of palatal fusion with mesenchymal confluence following injection at E12.5 (100%), E13.5 (100%), E14.5 (82%), and E15.5 (75%). Viral vectors injected into the amniotic sac transduced the most superficial and transient peridermal cell layer but not underlying basal epithelial cells. TGFβ3 transduction of the peridermdal cell layer was sufficient to induce adhesion, fusion, and disappearance of the palatal shelf MEE in a cell nonautonomous manner. We propose that in...Continue Reading

References

Feb 1, 1989·Developmental Biology·J E Fitchett, E D Hay
Dec 1, 1995·Nature Genetics·G ProetzelT Doetschman
Feb 7, 2001·Developmental Biology·C Martínez-AlvarezM W Ferguson
Sep 10, 2002·Nature Genetics·Shinji KondoJeffrey Clark Murray
Jan 15, 2004·Human Molecular Genetics·Philip Stanier, Gudrun E Moore
Jan 20, 2004·Developmental Biology·Marek DudasVesa Kaartinen
Feb 6, 2004·Plastic and Reconstructive Surgery·Naveen YalamanchiJames Chang
Feb 5, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Nadine S DejnekaJean Bennett
Jan 15, 2005·Developmental Biology·Xiao-Mei CuiCharles F Shuler
Jan 26, 2005·The Journal of Biological Chemistry·Tami L ThomaeChristopher A Bradfield
Jul 5, 2005·British Journal of Plastic Surgery·N A PapadopulosE Biemer
Aug 30, 2005·Journal of the American College of Surgeons·Leonard LuThomas A Mustoe
Oct 26, 2005·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Alexandra S KnightMichael J Dixon
Dec 6, 2005·Journal of the Society for Gynecologic Investigation·Cecilia Y Cheung, Robert A Brace
Sep 1, 2006·Developmental Biology·Amel Gritli-Linde
Oct 10, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·M EndoA W Flake
Apr 24, 2008·Differentiation; Research in Biological Diversity·Elena Martínez-SanzC Martínez-Alvarez
May 16, 2008·Journal of Human Genetics·Heiko ReutterElisabeth Mangold
Apr 7, 2009·Cell·Maddalena AdornoStefano Piccolo
May 15, 2009·Human Molecular Genetics·Rebecca J RichardsonMichael J Dixon
Aug 26, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Simon N WaddingtonTristan R McKay
Nov 15, 2011·Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology·P Martinez-TenW Sepulveda

Citations

Apr 14, 2016·Molecular Therapy. Methods & Clinical Development·Graça Almeida-PoradaChristopher D Porada
Dec 20, 2014·Developmental Biology·Jamie LaneVesa Kaartinen
Aug 18, 2017·Journal of Dental Research·K J LoughS E Williams
Nov 2, 2014·Journal of Cellular Physiology·Lihua HuAli Nawshad
Sep 4, 2015·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Youssef A Kousa, Brian C Schutte
Feb 12, 2015·Psychiatry Investigation·Mi Sook DohYoung Gyu Chai
Dec 30, 2017·Experimental and Therapeutic Medicine·Zheng JiangDongwei Xu
May 1, 2020·Current Stem Cell Reports·Martin RodriguezGraҫa Almeida-Porada

Related Concepts

Tgfb3 protein, mouse
Structure of Amnion
Metazoa
Cercopithecus tantalus
Cleft Palate, Isolated
Shuttle Vectors
Founder Mice, Transgenic
Transduction, Genetic
Zoophaginae
COS-7 Cells

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Barrett Esophagus

Barrett’s esophagus if a serious complication of gastroesophageal reflux disease during which the normal esophageal lining changes to tissue that resembles intestinal lining. Here is the latest research.