Riya Mishra
Research Mentor: Yuji Mishina
Mentor Department: Biological and Material Sciences, Dentistry
Author(s): Riya Mishra, Sher Khehra, Yuji Mishina
Session: Session 4 (1:00 PM – 1:50 PM)
Presentation Type: Poster 88
Abstract
Congenital tracheomalacia is a clinically significant airway disorder caused by abnormal development of tracheal cartilage, leading to airway collapse and respiratory distress in infants. While its structural consequences are well-characterized, the genetic factors underlying defective cartilage remain poorly understood. This project investigates the genetic contributions to congenital tracheomalacia during embryonic development. Mutations in the gene Evc2, also known as Limbin (Lbn), are known to cause abnormalities in tracheal cartilage development in humans and mice, but the mechanisms by which this gene alters development remain unknown. In normal development, C-shaped tracheal cartilage forms through condensation of tracheal mesenchyme. Previous research has revealed that Evc2 mutants exhibit abnormal tracheal mesenchymal condensation, resulting in malformed tracheal cartilage. Thus, spatial transcriptomic analysis of Evc2 mutant embryos at the mesenchyme condensation stage was set up, identifying several candidate genes with statistically significant changes in expression levels and locations compared to controls. This project focuses on characterizing these genes to determine whether their altered expression reflects delays in developmental timing, divergence from normal cellular development trajectories, or other regulatory disruptions associated with abnormal tracheal formation. Pregnant mice were dissected to collect embryos at defined developmental stages. DNA was extracted, and PCR was performed to genotype embryos for the mutated Evc2 gene. Embryos were embedded in frozen blocks, sectioned using a cryostat, and immunohistochemically stained. Sections were then analyzed microscopically to evaluate tracheal morphology and correlate structural changes with gene expression patterns. By integrating morphological analysis with candidate gene investigation, this work aims to clarify how altered gene expression influences developmental processes involved in tracheal cartilage formation and may contribute to improved genetic screening and early diagnosis of tracheomalacia and related airway disorders.
