Molecular determinants of placodal competence in non-neural ectoderm
The sense organs of the mammalian head and the anterior pituitary, a major endocrine gland, originate to a great extent from embryonic structures called cranial placodes. These placodes arise from the ectoderm, one of the three germ layers, which is known to give rise to brain, spinal cord, and epidermis. Placodes develop in the head of the embryo in a narrow region that is flanked by the developing brain and epidermis. Generation of placodal cells from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) has been difficult because as the stem cells differentiate into ectodermal cells, they favor developing into brain, spinal cord, or epidermis. This research project aims to understand the mechanisms that restrict but also enable ectodermal cells from developing into placodal cells. In a second aim, it is proposed to investigate the molecular mechanisms that enable placodal cells generated from hESCs/hiPSCs to develop into distinct placodal cell types. These distinct placodal lineages encompass cells that play crucial roles in smell, vision, hearing, balance, touch, pain, and endocrine processes such as growth, reproduction, lactation, and stress. The overarching goal of the research is to provide a deeper understanding of the molecular mechanisms that can be used to advance human stem cell-based applications to numerous sensory as well as endocrinological disorders.
Millions of Californians suffer from disorders of the sensory and endocrinological systems of the head. These disorders range from the loss of smell, chronic sinusitis, vision loss, hearing loss, tinnitus, vertigo, touch perception disorders, chronic pain, and endocrinological dysfunction. Although most of these disorders to not directly cause death, they can contribute to morbidity and they play substantial roles in diminishing the quality of life, especially in an aging population. The US statistics for each individual of these disorders reveals that they affect a large percentage of the population, which reflected to the state of California means millions of people costing the health care system multiple billions of dollars each year.
Quality of life interventions for the aging population are a major market, and biological as well as pharmacological interventions arising from the proposed research has the potential to create jobs in the biotech and pharmaceutical industry. The Principal Investigator has previous experience of licensing discoveries made in his laboratory to industrial partners located in CA, which already led to creation of new jobs and the potential to bring novel treatments that would help millions of Californians to live healthier and longer lives.