Identifying the mechanism critical for proliferation, apoptosis, and cell-cell interaction in the development of mouse adrenals and gonads

adrenal;adrenal medulla;testis;ovary;Sonic hedgehog;Dicer1;miRNA

Huang, Chen-Che J.

关键词: adrenal;    adrenal medulla;    testis;    ovary;    Sonic hedgehog;    Dicer1;    miRNA;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/18615/Huang_Chen-Che.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Adrenal, testis, and ovary are steroidogenic organs derived from a common primordium that consists of Steroidogenic factor 1 (SF1)-positive precursor cells. SF1 not only defines the steroidogenic lineages in these organs, but also controls their differentiation. In this thesis project, I used Sf1/Cre transgenic mice to generate different types of knockout models to study the development of Sf1-positive cells in mice. My study is specifically focused on (1) the contribution of adrenal capsular cells to the SF1-positive cortical cells; (2) the maintenance of SF1-positive cells; and (3) the interaction between SF1-positive adrenal cortical cells and adrenal medulla cells. Recent evidence implicates the Hedgehog (Hh) signaling pathway is involved in the appearance of steroidogenic cells in these organs. The Hh signaling pathway serves as a common crosstalk component and yet evolves diverse functions in the expansion and differentiation of the steroidogenic cells in a tissue-specific manner. In Chapter 2, I provided evidence showing that Sonic hedgehog (Shh) from adrenal cortical cells elicits its function on adrenal capsular cells, which contribute to the adrenal cortex population. Ablation of Shh in the differentiated cortical cells results in decreased proliferation of the undifferentiated capsular cells. Other than Hh signaling, microRNA machinery is also involved in the development of SF1-positive cells. In Chapter 3, I demonstrated a tissue-specific requirement of Dicer1, the key enzyme for microRNA biosynthesis, among adrenal, testis and ovary. Adrenal cortical cells, Sertoli cells and Leydig cells show different sensitivity to the loss of Dicer1. Although Dicer1 was removed at the same time in these SF1-positive cells during development, these tissues underwent apoptosis at later different stages. In Chapter 4, the goal of this study was to investigate whether abnormal development of the adrenal cortex affects the differentiation of the adrenal medulla in mice. I used four mouse models with different types of defects in adrenal cortex to show that a well developed adrenal cortex is not required for adrenal medulla growth.