Date of Award


Degree Type


Degree Name

Master of Science (MS)





Formation of skeletal structural elements during vertebrate embryogenesis is largely a

conserved evolutionary process that employs numerous conserved genes and pathways. One

critical gene in this process is the highly conserved vertebrate Type II Collagen alpha 1 (col2α1).

It produces multiple splice isoforms that have different functions and expression patterns during

skeletogenesis. Two of the primary isoforms are of great interest; variant 1, the primary

embryonic isoform, and variant 2, a post embryonic isoform. While the more commonly known

post-embryonic isoform has been well studied over the last 30 years, identification of a unique

role for the evolutionarily conserved embryonic isoform has remained elusive, even though some

evidence has suggested its importance during early development. The objective of this study is to

identify whether the highly conserved embryonic isoform of col2α1 which contains a conserved

von Willibrand Factor Type-C (vWFC) domain may serve a role in addition to its known

structural function during development.

To investigate these potential non-structural function(s) of the conserved col2α1 during

embryogenesis, we utilized the model organism Danio rerio, the zebrafish. Other laboratories

have identified in other proteins containing conserved vWFC domain(s) as having a role in

morphogen gradient regulation, specifically in dorsoventral patterning of developing vertebrate

embryos. To investigate this possibility, we executed a three-phased plan to knockout,

overexpress, and knockdown the conserved embryonic isoform that contains the conserved

vWFC domain to determine its requirement during organogenesis. Our results demonstrate thatxii

the knockdown of the embryonic isoform of col2α1 results in abnormalities in formation of

craniofacial cartilage and/or tail/trunk structures beginning at the time that col2α1 becomes

active during embryogenesis and results in some embryos with similar phenotypes and issues

potentially related to dysregulation of TGF-β morphogen gradients.

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Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Available for download on Wednesday, January 17, 2024

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