1. The secreted protein, Sonic hedgehog (Shh), plays essential roles in establishing the ventral patterning of the vertebrate central nervous system (CNS). In the absence of Shh function, the normal processes to form neural tube are impaired resulting in holoprosencephaly (HPE), a structural malformation of the brain, as well as neuronal patterning and path finding defects. It is integral to study how Shh transcription is regulated in the CNS for the understanding of ventral neural tube development. Research in my laboratory focuses on uncovering the cis and trans acting determinants of Shh expression in the mouse CNS through employing genetic, genomic and biochemical approaches. An understanding of how Shh expression is initiated in the ventral forebrain may provide insight into additional causes of holoprosencephaly.

2. Molecular interactions coordinating the forebrain development Zona Limitans Intrathalamica (ZLI) is the interface between territories, thalamus and prethalamus, that are structurally and functionally different. The ZLI has been implicated as a local forebrain signaling center controlling the proliferation and fate of the thalamic neurons. The ZLI colocalizes with the junction of unique gene expression domains, and is marked by distinct signals including Sonic Hedgehog (SHH), Wnt and Fgf. Little is, however, known of the molecular events underlying the function and formation of the ZLI. To address the molecular mechanism how distinct signals such as Notch, Wnt, SHH and Fgf are induced and integrated to form the ZLI, I will attempt to identify the upstream transcription factors responsible for initiating the signals in the prospective ZLI. In parallel, using ZLI-specific Cre driver, I will also attempt to conditionally inactivate SHH and Wnt in order to ask how these signaling pathways coordinate to form the developing ZLI and thalamic neurons.

1. Cho M, Ryu M, Jeong Y, Chung YH, Kim DE, Cho HS, Kang S, Han JS, Chang MY, Lee CK, Jin M, Kim HJ, Oh S (2009) Cardamonin suppresses melanogenesis by inhibition of Wnt/beta-catenin signaling. Biochem Biophys Res Commun. [Epub ahead of print]

2. Gwak J, Song T, Song JY, Yun YS, Choi IW, Jeong Y, Shin JG, Oh S (2009) Isoreserpine promotes beta-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells. Biochem Biophys Res Commun 387(3):444-9

3. Jeong Y, Leskow FC, El-Jaick K, Roessler E, Muenke M, Yocum A, Dubourg C, Li X, Geng X, Oliver G, Epstein DJ (2008) Regulation of a remote Shh forebrain enhancer by the Six3 homeoprotein. Nat Genet 40(11):1348-53

4. Geng X, Speirs C, Lagutin O, Inbal A, Liu W, Solnica-Krezel L, Jeong Y, Epstein DJ, Oliver G (2008) Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in the ventral forebrain and causes holoprosencephaly. Dev Cell 15(2):236-47

5. Ruzhynsky VA, McClellan KA, Vanderluit JL, Jeong Y, Furimsky M, Park DS, Epstein DJ, Wallace VA, Slack RS (2007) Cell cycle regulator E2F4 is essential for the development of the ventral telencephalon. J Neurosci 27(22):5926-35.

6. Pachikara A, Dolson DK, Martinu L, Riccomagno MM, Jeong Y, Epstein DJ (2007) Activation of Class I transcription factors by low level Sonic hedgehog signaling is mediated by Gli2-dependent and independent mechanisms. Dev Biol 305(1):52-62

7. Park ES, Choi S, Kim JM, Jeong Y, Choe J, Park CS, Choi Y, Rho J (2007) Early embryonic lethality caused by targeted disruption of the TRAF-interacting protein (TRIP) gene. Biochem Biophys Res Commun 363(4):971-7.

8. Lei Q, Jeong Y, Misra K, Li S, Zelman AK, Epstein DJ, Matise MP (2006) Wnt signaling inhibitors regulate the transcriptional response to morphogenetic Shh-Gli signaling in the neural tube. Dev Cell 11(3):325-37

9. Jeong Y, El-Jaick K, Roessler E, Muenke M, Epstein DJ (2006) A functional screen for sonic hedgehog regulatory elements across a 1 Mb interval identifies long-range ventral forebrain enhancers. Development 133(4):761-72.

10. Jeong Y, Epstein DJ (2005) Modification and production of BAC transgenes. Curr Protoc Mol Biol Chapter 23:Unit 23.11.

11. Jeong Y, Epstein DJ (2003) Distinct regulators of Shh transcription in the floor plate and notochord indicate separate origins for these tissues in the mouse node. Development. 130(16):3891-902

12. Jeong Y, Won J, Kim C, Yim J (2000) 5'-Flanking sequence and promoter activity of the rabbit neuronal nitric oxide synthase (nNOS) gene. Mol Cells 10(5):566-74.

13. Jeong Y, Won J, Yim J (1998) Cloning and structure of a rabbit protein inhibitor of neuronal nitric oxide synthase (PIN) gene and its pseudogene. Gene 214(1-2):67-75.