題目：Transcriptomopathies: A Window on the Earliest Developmental Origins of Birth Defects
講員：Anne L. Calof, Ph.D.
Professor, Depts of Anatomy & Neurobiology, Developmental & Cell Biology, and Center for Complex Biological Systems, University of California Irvine
時間：2023年1月5日（星期四）上午10:30
地點：臺大心理系北館北A教室
簡介：
We study birth defect development using animal models of Cornelia de Lange Syndrome, a global birth defects syndrome caused by haploinsufficiency for Nipbl. Strikingly, we have found recently that Nipbl+/- embryos dramatically overexpress Nanog, a transcriptional repressor required for stem cell pluripotency in pre-implantation embryos, and which is normally transiently re-expressed, and then shut down, during gastrulation. In Nipbl+/- mice, Nanog fails to shut off appropriately post-gastrulation, and its levels are many-fold above normal. Interestingly, this results in changes in the expression of crucial developmental genes that are also known targets of Nanog: these include (a) genes associated with pluripotency (Pou5f1/Oct4); (b) genes that control left-right patterning (Tdgf1, Lefty2, Nodal) and anterior-posterior patterning (Hox genes); and (c) genes that regulate primitive erythropoiesis (Tal1, Lmo2, Hbb-bh1). Accompanying these gene expression changes are changes in the allocation of cells to different stem cell populations in the early embryo, including cardiac stem cells and neural crest stem cells. These results suggest that a failure to downregulate Nanog expression after gastrulation, and the transcriptional dysregulation that ensues, lead to misallocation and global dysfunction of stem cell populations and ensuing development of syndromic structural birth defects.
主辦單位：國立臺灣大學神經生物與認知科學研究中心、生物技術研究中心