Biology & Sustainability
The Effects of Epigallocatechin gallate (EGCG) on Cellular and Molecular Craniofacial Precursors
Document Type
Poster Presentation
Location
Indianapolis, IN
Subject Area
Biology & Sustainability
Start Date
11-4-2014 8:30 AM
End Date
11-4-2014 9:30 AM
Sponsor
Randall Roper (Indiana University/Purdue University at Indianapolis)
Description
Down Syndrome (DS), also known as trisomy 21, is a genetic disorder caused by an extra copy of human chromosome 21. Individuals with DS exhibit various phenotypes such as cognitive, skeletal and craniofacial abnormalities. The Ts65Dn mouse model displays similar craniofacial abnormalities as observed in humans with DS including a small, undersized mandible. To gain a better understanding of craniofacial abnormalities, we study the molecular and cellular mechanisms underlying these abnormalities. Previous studies conducted in our lab identified a deficit in neural crest (NC) cells in the first pharyngeal arch (PA1) or mandibular precursor. Ts65Dn mice at embryonic day 9.5 (E9.5) had a smaller PA1, due to reduced proliferation, generation, and migration of NC cells when compared to normal age matched controls. We hypothesize that an inherent molecular mechanism responsible for the small, undersized mandible is overexpression of Dyrk1a, a gene that is found in three copies in individuals with DS and Ts65Dn mice. Epigallocatechin gallate (EGCG), a green tea polyphenol, is known to inhibit Dyrk1a activity. To test our hypothesis, we treat the embryos with EGCG in utero. We experiment with two treatment regimens. We treat Ts65Dn mothers by oral gavage with a high dose of EGCG on embryonic day 7 and 8 (E7-E8) or a lower dose of EGCG administered ad libitum from E0-E9.5. By using unbiased stereology, we will be able to predict which treatment is better able to ameliorate NC cell deficits. Our results for the E7-E8 treatment group have shown an increase in NC cells and PA1 volume. We will continue to examine the molecular and cellular effects of EGCG on the developing PA1. We expect to find a larger overall embryonic size, a larger PA1 size and increased PA1 NC cells.
The Effects of Epigallocatechin gallate (EGCG) on Cellular and Molecular Craniofacial Precursors
Indianapolis, IN
Down Syndrome (DS), also known as trisomy 21, is a genetic disorder caused by an extra copy of human chromosome 21. Individuals with DS exhibit various phenotypes such as cognitive, skeletal and craniofacial abnormalities. The Ts65Dn mouse model displays similar craniofacial abnormalities as observed in humans with DS including a small, undersized mandible. To gain a better understanding of craniofacial abnormalities, we study the molecular and cellular mechanisms underlying these abnormalities. Previous studies conducted in our lab identified a deficit in neural crest (NC) cells in the first pharyngeal arch (PA1) or mandibular precursor. Ts65Dn mice at embryonic day 9.5 (E9.5) had a smaller PA1, due to reduced proliferation, generation, and migration of NC cells when compared to normal age matched controls. We hypothesize that an inherent molecular mechanism responsible for the small, undersized mandible is overexpression of Dyrk1a, a gene that is found in three copies in individuals with DS and Ts65Dn mice. Epigallocatechin gallate (EGCG), a green tea polyphenol, is known to inhibit Dyrk1a activity. To test our hypothesis, we treat the embryos with EGCG in utero. We experiment with two treatment regimens. We treat Ts65Dn mothers by oral gavage with a high dose of EGCG on embryonic day 7 and 8 (E7-E8) or a lower dose of EGCG administered ad libitum from E0-E9.5. By using unbiased stereology, we will be able to predict which treatment is better able to ameliorate NC cell deficits. Our results for the E7-E8 treatment group have shown an increase in NC cells and PA1 volume. We will continue to examine the molecular and cellular effects of EGCG on the developing PA1. We expect to find a larger overall embryonic size, a larger PA1 size and increased PA1 NC cells.