Genome organizer SATB1 function in salivary gland and development and growth

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Project Summary/Abstract Salivary glands produce saliva, which facilitates digestion, acts as a lubricant to swallow foods, and prevents infections in oral cavity and tooth decay. Therefore, salivary gland function is important for oral health. Currently, there is no effective treatment for impaired salivary glands, which can be caused by therapeutic irradiation for the head and neck cancer or autoimmune diseases. To develop therapeutic strategies in the future, it is essential to understand the regulatory mechanisms underling development of salivary glands and their regeneration. Little is known about the regulators of gene expression, epigenetics and chromatin organization for salivary glands. Here, we will test a hypothesis that the genome organizer SATB1 is a critical regulator in salivary gland embryonic development, early postnatal growth and development, and function. This hypothesis is supported by SATB1 protein being expressed in both acinar and ductal cells at postnatal day 12 (P12) of wild-type mice and by detection of much smaller salivary glands in Satb1-/- mice compared to wild-type mice. We will identify SATB1 protein-expressing cells in SGs during embryonic and postnatal development. By genetic lineage tracing, we will study the role of SATB1 in acinar cell development and function. We will delete SATB1 in acinar cell- specific cell lineages (e.g. AQPT5+ or MIST1+ cells) at specific time points and determine the effects of SATB1 ablation in their descendants. Through these experiments, we will learn the roles of SATB1 in proliferation, morphogenesis, survival and growth during embryonic and early postnatal development. In addition, combining the lineage-tracing approach with Global run-on sequencing (GRO-seq), which captures nascent transcripts, we will identify genes regulated by SATB1 in a cell lineage-specific and stage-specific manner. We expect that results from these proposed experiments will uncover the critical contribution of SATB1 in salivary gland development, growth and function, and such information will likely provide the foundation for the future therapeutic design to promote salivary gland regeneration.