Kate Weidig
Pronouns: she/her
Research Mentor(s): Gary Hammer
Research Mentor School/College/Department: Internal Medicine MEND / Medicine
Program: UROPF
Session: Session 3 (11:00am – 11:50am)
Authors: Kate Weidig , Yulan Chu
Abstract
The adrenal glands, specifically the adrenal cortex, are essential to producing steroidogenic hormones. The cortex can be divided into three layers: the outermost Zona Glomerulosa, the intermediate Zona ??Fasciculata, and the innermost layer, the Zona Reticularis, which are associated with mineralocorticoids, glucose homeostasis, and androgens, respectively. In order to sustain the production of steroid hormones, steroidogenic cells must be continuously replenished through the balance between cell proliferation, cell differentiation, and centripetal migration. Adrenocortical progenitor cells are vital to said balance as they possess the ability of self-renewal proliferation as well as the potential to differentiate into steroidogenic lineages. Dysregulation of this homeostasis within the cortex is associated with several adrenal diseases including Pallister-Hall syndrome, congenital adrenal hypoplasia, and SERKAL syndrome. SF1 can be phosphorylated on serine 203 and this phosphorylation has been shown to regulate the capacity of SF1 to function as a transcriptional factor. Overall, our hypothesis is that SF1 phosphorylation regulates the fate decision of Shh-expressing progenitor cells during adrenal homeostasis. To investigate this hypothesis, we newly engineered SF1 S203 phospho-mimic SF1-S203D and non-phosphorylatable SF1-S203A mouse models. We used mouse models of Shh-LacZ and Shh- CreERT2; R26mTmG. By crossing S203A/D mice with an Shh-LacZ reporter strain, we are able to visualize Shh-expressing progenitor cells. We introduced SHH-CREERT2; R26MTMG lineage tracing system to S203A/D mice to follow the fate of individual progenitor cells. Our results show that SF1 phosphorylation can keep the progenitor cells in an undifferentiated self-renewal state.
