Forebrain stem cell development, disease, and application – During mammalian forebrain development, neural stem cells (NSCs) adopt a number of unique cell fates. Two of these are the choroid plexus, the source of cerebrospinal fluid (CSF), and the cerebral cortex, the seat of our higher cognitive and neurologic functions. The mechanisms used to make cortical and choroid plexus cells and their borders remain fundamental questions in neuroscience. Moreover, when these structures form improperly, common disorders such as hydrocephalus, mental retardation, and epilepsy too often ensue.
The goal of our lab is to understand how these forebrain cell types are formed and separated, then apply this information to human disorders and NSC culture strategies aimed at potential cell-based therapies. Current studies focus on the roles of morphogens and transcription factors in early NSC fate control and boundary formation, and translational approaches using our recently-patented method for deriving choroid plexus epithelial cells from mouse and human embryonic stem cells (ESCs). Approaches used in the lab include cell cultures of mouse and human ESCs and NSCs, explants, mouse genetics, mouse models of human disease, in utero electroporation, cell injections, and systems biology/mathematical modeling of early forebrain development together with UCI collaborators.
- Lun MP, Monuki ES, Lehtinen MK. (2015) Development and functions of the choroid plexus-cerebrospinal fluid system. Nat Rev Neurosci Jul 15. doi: 10.1038/nm3921 [Epub ahead of print]. (Review).
- Hong T, Fung ES, Zhang L, Huynh G, Monuki ES, Nie Q. (2015) Semi-adaptive response and noise attenuation in BMP signaling. J R Soc Interface 12(107). pii: 20150258. doi: 10.1098/rsif.2015.0258.
- Striedter GF, Srinivasan S, Monuki ES. (2015) Cortical Folding: When, Where, How, and Why? Annu Rev Neurosci 38:291-307. (Review).
- Barkho BZ, Monuki ES. (2015) Proliferation of cultured mouse choroid plexus epithelial cells. PLoS One 10(3):e0121738.
- Lun MP, Johnson MB, Broadbelt KG, Watanabe M, Kang Y-J, Chau KF, Springel MW, Malesz A, Sousa AM, Pletikos M, Adelita T, Calicchio ML, Zhang Y, Holtzman MJ, Lidov HG, Šestan N, Steen H, Monuki ES, Lehtinen MK. (2015) Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional cerebrospinal fluid production. J Neurosci 35(12):4903-4916.
- Chinn GA, Hirokawa KE, Chuang TM, Urbina C, Patel F, Fong J, Funatsu N, Monuki ES. (2014) Agenesis of the corpus callosum due to defective glial wedge formation in Lhx2 mutant mice. Cereb Cortex [Epub ahead of print].
- Srinivasan S, Hu JS, Currle DS, Fung ES, Hayes WB, Lander AS, Monuki ES. (2014) A BMP-FGF morphogen toggle switch drives the ultrasensitive expression of multiple genes in the developing forebrain. PLoS Comp Biol 10(2):e1003463.
- Lehtinen M, Bjornsson CS, Dymecki SM, Gilbertson RJ, Holtzman DM, Monuki ES. (2013) The choroid plexus and cerebrospinal fluid: emerging roles in development, disease, and therapy. J Neurosci 33(45):17553-9. (Review).
- Watanabe M, Kang Y-J, Davies LM, Meghpara S, Lau K, Chung C-Y, Kathirya J, Hadjantonakis A-K, Monuki ES. (2012) BMP4 sufficiency to induce choroid plexus epithelial fate from embryonic stem cell-derived neuroepithelial progenitors. J Neurosci 32(45):15934-15945. (Cover illustration).
- Doan LT, Javier AL, Furr NM, Nguyen KL, Cho KW, Monuki ES. (2012) A Bmp reporter with ultrasensitive characteristics reveals that high Bmp signaling is not required for cortical hem fate. PLoS One 7(9):e44009.
- Javier AL, Doan LT, Luong M, de Mochel NSR, Sun A, Monuki ES, Cho KWY. (2012) BMP indicator mice reveal dynamic regulation of transcriptional response. PLoS One 7(9):e42566.
- McGowan L, Kuo E, Martin A, Monuki ES, Striedter G. (2011) Species differences in early patterning of the avian brain. Evolution 65(3):907-11.
- Mangale VS, Hirokawa KE, Satyaki PRV, Gokulchandran N, Chickbire S, Subramanian L, Shetty AS, Martynoga B, Paul J, Mai MV, Li Y, Flanagan LA, Tole S, Monuki ES. (2008) Lhx2 selector activity specifies cortical identity and suppresses hippocampal organizer fate. Science 319:304-9. (Research Article).
- Hu JS, Doan LT, Currle DS, Paff M, Rheem JY, Schreyer R, Robert B, Monuki ES. (2008) Border formation in a Bmp gradient reduced to single dissociated cells. Proc Natl Acad Sci U S A 105(9):3398-403.
- Flanagan LA, Lu J, Wang L, Marchenko SA, Jeon NL, Lee AP, Monuki ES. (2008) Unique dielectric properties distinguish stem cells and their differentiated progeny. Stem Cells 26(3):656-65.
- Monuki ES (2007) The morphogen signaling network in forebrain development and holoprosencephaly. J Neuropathol Exp Neurol 66(7):566-75. (Review).
- Cheng X, Hsu CM, Currle DS, Hu JS, Barkovich AJ, Monuki ES. (2006) Central roles of the roof plate in telencephalic development and holoprosencephaly. J Neurosci 26:7640-7649.
- Currle DS, Hsu CM, Cheng X, Monuki ES. (2005) Direct and indirect roles of CNS dorsal midline cells in choroid plexus epithelia formation. Development 132:3549-3559.