Author ORCID Identifier


Date of Graduation


Document Type

Dissertation (PhD)

Program Affiliation

Cancer Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Jian Hu, PhD

Committee Member

Ambro Van Hoof, PhD

Committee Member

Juan Fueyo, MD

Committee Member

Yejing Ge, PhD

Committee Member

Jichao Chen, PhD

Committee Member

Jeffrey Chang, PhD


The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional deletion of Med12 recapitulated clinical observations in XLID (X-Linked Intellectual Disability) patients with Med12 loss-of-function mutations. In the present study, we establish the role of Med12 in 1) de novo myelin synthesis in the central nervous system, 2) myelin maintenance in the adult peripheral nervous system, and finally, 3) pigmentation ability of hair melanocytes. Our models provide novel molecular functions and downstream targets of Med12, with a special emphasis on cells of neural crest origin. Moreover, our models constitute versatile in vivo tools for future studies by reliably modeling a variety of pathologies presented in multiple neurological syndromes, including but not limited to developmental intellectual disability syndromes, demyelination-induced peripheral neuropathies, and depigmentation disorders.


MED12, Mediator complex, Myelin, XLID, Demyelination, Peripheral Nervous System, Central Nervous Sytem, CNS, PNS, Melanocytes, Schwann Cells



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