Archita Girmannagari
Pronouns: she/her/hers
Research Mentor(s): Yuji Mishina
Co-Presenter:
Research Mentor School/College/Department: Biological and Material Sciences / Dentistry
Presentation Date: April 20
Presentation Type: Poster
Session: Session 4 – 2:40pm – 3:30 pm
Room: League Ballroom
Authors: Archita Girmannagari, Hiroki Ueharu, Yuji Mishina
Presenter: 37
Abstract
Cranial neural crest cells (NCCs) are migratory, multipotent cells that differentiate into numerous structures in the facial region. Abnormal behaviors of cranial neural crest cells in their proliferation, migration, cell fate specification, and subsequent differentiation can result in craniofacial, including mid facial, deformities. Growth factor signaling, especially by that of Bone morphogenetic proteins (BMPs), regulates these processes. Our group and other found that the effects of BMP signaling are dependent by factors such as different tissues, cell types, stages of development, and/or pathophysiologic conditions. To understand the functions of BMP signaling during cranial NCC development, we generated two lines of transgenic mice using the same transgenic DNA construct. We expected that expression levels and patterns of the transgene will slightly differ between the two lines due, in part, to the integration sites in the whole genome. Thus, they will be invaluable tools to understand mechanisms of context dependent functions of BMP signaling. Our transgenic construct is to express a gain-of-function mutant type 1 receptor for BMPs (caAcvr1) after Cre recombination. We have generated two mouse lines, line L35 and line A11, and bred with neural crest-specific Cre mouse line, P0-Cre line, to enhance BMP signaling in neural crest derived tissues. Both lines demonstrated severe craniofacial deformities. However, in the L35 line, we found ectopic cartilage formation while the A11 line developed a mid facial cleft with relatively normal bones and cartilage. The abnormal location of cartilage formation could indicate aberrant cell specification of multi-potent cranial NCCs due to enhanced BMP signaling. Subsequent molecular analyses revealed that the L35 line showed increased Xist expression leading to ectopic X chromosome inactivation (XCI), which is never observed during normal development. The aim of this study is to gain supporting evidence that ectopic XCI is the reason for ectopic cartilage formation in the L35 line. For this study, we quantified levels of Xist expression and investigated the number cells showing ectopic XCI in the A11 line and compared with those found in line L35. The conclusion of this study will either confirm or deny our hypothesis that ectopic XCI influences cell fate specification in cranial NCCs.
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences
