Abstract

Crosstalk between Fibroblast Growth Factors (FGFs) and Sonic hedgehog (SHH) is essential for proper limb development; however, the molecular mechanisms involved in this process remain unclear. Via comparative transcriptome analysis and gene knockdown and overexpression studies, we identified the transcription factor Lim homeobox 2 (LHX2) as an intermediate in FGF-directed SHH expression. We determined that FGF signaling was necessary for LHX2 expression and demonstrated that LHX2 is a primary transcription target of FGF signaling through the RAS and AKT pathways. Additionally, loss of LHX2 in the distal limb results in decreased SHH expression and a truncated limb within 24 hours of treatment, while overexpression of LHX2 in the presence of ectopic FGF leads to increased SHH expression. While LHX2 is insufficient alone to induce SHH, we conclude that it likely serves as a competency factor for endogenous SHH expression, keeping it juxtaposed to the distal apical ectodermal ridge during limb outgrowth.

LLU Discipline

Microbiology and Molecular Genetics

Department

Microbiology

School

School of Medicine

First Advisor

Kerby C. Oberg

Second Advisor

Hansel M. Fletcher

Third Advisor

Susan Mackem

Fourth Advisor

Subburaman Mohan

Fifth Advisor

Charles Wang

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2018

Date (Title Page)

8-2018

Language

English

Library of Congress/MESH Subject Headings

Transcription Factors; Fibroblast Growth Factors; LIM-Homeodomain Proteins; Proto-Oncogene Proteins c-akt; Gene Knockdown Techniques; Transcriptome

Type

Dissertation

Page Count

x, 116 p.

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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