Date of Award

1998

Document Type

Restricted Thesis

Terms of Use

© 1998 Jason Bromer. All rights reserved. Access to this work is restricted to users within the Swarthmore College network and may only be used for non-commercial, educational, and research purposes. Sharing with users outside of the Swarthmore College network is expressly prohibited. For all other uses, including reproduction and distribution, please contact the copyright holder.

Degree Name

Bachelor of Arts

Department

Biology Department

First Advisor

Judith Cebra-Thomas

Second Advisor

Scott F. Gilbert

Abstract

The T-box family is an evolutionarily conserved group of genes, each of which shares a region encoding a DNA-binding domain similar to that encoded by the Brachyury gene (T). T-box gene expression shows temporal and spatial variation in the developing mouse embryo. A subfamily of these genes contains Tbx4 and Tbx5, which are very similar to each other. Tbx4 and Tbx5 are generally co-expressed, but they are differentially expressed in the limbs, suggesting a role in fore/hindlimb differentiation. In addition to limb expression, Tbx4 and Tbx5 are also specifically expressed in the developing lungs, and are believed to play a role in lung development and branching. We have cloned a putative homolog of this subfamily in chickens that appears to more closely resemble mTbx5 than mTbx4 in limb expression. Consistent with other recent findings, these expression patterns suggest a conserved role for the T-box genes in the mechanisms of limb development in different tetrapods. I also show here that Tbx4 and/or Tbx5 also are involved in the normal branching morphogenesis of developing chick lung epithelium. Since these T-box genes are thought to encode transcription factors expressed in the mesenchyme, I have also looked at downstream effects of T-box inhibition that might be mediated by mesenchymal/epithelial paracrine factors. I report that these T-box genes appear to regulate the expression of chick sonic hedgehog (cShh), another gene that has been implicated in the pathway of normal branching morphogenesis. These data suggest a possible pathway through which the Tbx4 and Tbx5 subfamily could regulate lung epithelial branching morphogenesis in the developing chicken by regulating members of the Fibroblast Growth Factor (FGF) family of paracrine factors. The FGF proteins in turn regulate the induction of epithelial branching through Shh.

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