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University of Texas – Austin

1. -1021-0306. Mechanisms directing chondrocyte specification in the developing limb.

Degree: Cellular and Molecular Biology, 2018, University of Texas – Austin

During limb development, skeletal elements originate from highly proliferative mesodermal progenitor cells that differentiate into chondrocytes. While this process must be tightly regulated to ensure proper size and specialization of cartilage elements, the mechanisms behind the maintenance of mesodermal progenitor cells and the initiation of differentiation is poorly understood. Bone morphogenetic proteins (BMPs) are early drivers of chondrogenesis, promoting compaction and the initiation of differentiation, but their biological role in limb development remains controversial. To address both the mechanism and timing of BMPs role in chondrogenesis we created a new mouse model to inhibit overall BMP signaling in the limb. With reduced BMP signaling during a precise 24-hour time window there is increased proliferation and delayed differentiation leading to polydactyly. Additionally, in an effort to identify regulators of chondroprogenitor cell maintenance, we found that PRMT5, a protein arginine methytransferase essential for stem cell pluripotency, is dynamically expressed in the distal undifferentiated limb. We found that loss of PRMT5 in the limb results in apoptosis of distal chondroprogenitor cells leading to severe limb truncations and unique autopod defects. We show that PRMT5 is essential for the maintenance of chondroprogenitor cells in the limb. Advisors/Committee Members: Vokes, Steven Alexander (advisor), Wallingford, John (committee member), Gross, Jeff (committee member), Macdonald, Paul (committee member), Ehrlich, Lauren (committee member).

Subjects/Keywords: BMP; Prmt5; Limb development; Polydactyly; Chondrogenesis; Chondroprogenitor; Gremlin; Sox9

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APA (6th Edition):

-1021-0306. (2018). Mechanisms directing chondrocyte specification in the developing limb. (Thesis). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/68374

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

-1021-0306. “Mechanisms directing chondrocyte specification in the developing limb.” 2018. Thesis, University of Texas – Austin. Accessed December 16, 2018. http://hdl.handle.net/2152/68374.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

-1021-0306. “Mechanisms directing chondrocyte specification in the developing limb.” 2018. Web. 16 Dec 2018.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

-1021-0306. Mechanisms directing chondrocyte specification in the developing limb. [Internet] [Thesis]. University of Texas – Austin; 2018. [cited 2018 Dec 16]. Available from: http://hdl.handle.net/2152/68374.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

-1021-0306. Mechanisms directing chondrocyte specification in the developing limb. [Thesis]. University of Texas – Austin; 2018. Available from: http://hdl.handle.net/2152/68374

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

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