Julie A. Siegenthaler

University of Colorado Denver

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Samuel J. Pleasure

University of California, San Francisco

Hannah E. Jones

Emory University

Stephanie Bonney

Seattle Children's Hospital

Christina N. Como

University of Colorado Denver

Rebecca O’Rourke

University of Colorado Anschutz Medical Campus

Bradley Pawlikowski

University of Colorado Anschutz Medical Campus

Youngshik Choe

Korea Brain Research Institute

Michael W. Miller

SUNY Upstate Medical University

Julia Derk

University of Colorado Anschutz Medical Campus

Swati Mishra

University of Washington

Cooperative Institutions

University of Colorado Anschutz Medical Campus

University of Colorado Denver

University of California, San Francisco

Stanford University

Harvard University

The Medical Center of Aurora

Centre National de la Recherche Scientifique

Tsinghua University

University of Colorado Boulder

Pediatrics and Genetics

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Gene Expression Profiling of Transporters in the Solute Carrier and ATP-Binding Cassette Superfamilies in Human Eye Substructures

Molecular Pharmaceutics (2012)

Amber Dahlin Ethan G. Geier Sophie L. Stocker Cheryl D. Cropp Elena Grigorenko

The barrier epithelia of the cornea and retina control drug and nutrient access to various compartments of the human eye. While ocular transporters are likely to play a critical role in homeostasis and drug delivery, little is known about their expression, localization and function. In this study, the mRNA expression levels of 445 transporters, metabolic enzymes, transcription factors and nuclear receptors were profiled in five regions of the human eye: cornea, iris, ciliary body, choroid and retina. Through RNA expression profiling and immunohistochemistry, several transporters were identified as putative targets for drug transport in ocular tissues. Our analysis identified SLC22A7 (OAT2), a carrier for the antiviral drug acyclovir, in the corneal epithelium, in addition to ABCG2 (BCRP), an important xenobiotic efflux pump, in retinal nerve fibers and the retinal pigment epithelium. Collectively, our results provide an understanding of the transporters that serve to maintain ocular homeostasis and which may be potential targets for drug delivery to deep compartments of the eye.

Solute carrier family

Abcg2

Choroid

Efflux

10.1021/mp300429e

Cite

Citations (55)

Single-Cell Transcriptomic Analyses of the Developing Meninges Reveal Meningeal Fibroblast Diversity and Function

Developmental Cell (2020)

John DeSisto Rebecca O’Rourke Hannah E. Jones Bradley Pawlikowski Alexandra D. Malek

Meninges

10.1016/j.devcel.2020.06.009

Cite

Citations (162)

There's No Place Like Home for a Neural Stem Cell

Cell stem cell (2010)

Julie A. Siegenthaler Samuel J. Pleasure

Lineage (genetic)

Ependymal Cell

Stem cell niche

Precursor cell

Cell lineage

10.1016/j.stem.2010.07.001

Cite

Citations (11)

Retinoic Acid Regulates Endothelial β-catenin Expression and Pericyte Numbers in the Developing Brain Vasculature

Frontiers in Cellular Neuroscience (2018)

Stephanie Bonney Brenna J. C. Dennison Megan Wendlandt Julie A. Siegenthaler

The acquisition of brain vascular properties, like tight junctions and pericytes, to form the blood-brain barrier (BBB) is crucial for a properly functioning central nervous system (CNS). Endothelial WNT signaling is a known driver of brain vascular development and BBB properties, however, it is unclear how endothelial WNT signaling is regulated. We recently showed that mouse embryos with disruptions in endothelial retinoic acid (RA) signaling have ectopic WNT signaling in the brain vasculature. Using immunohistochemistical analysis, we show that increased vascular WNT signaling in RA mutants (Pdgfbicre; dnRAR403-flox and Rdh10 mutants) is associated with elevated expression of the WNT transcriptional effector, β-catenin, in the brain endothelium. In vitro immunocytochemistry and proximity ligation studies in brain endothelial cells reveal that RA, through its receptor RARα, regulates β-catenin expression in brain endothelial cells via transcriptional suppression and phosphorylation events that targets β-catenin for proteasomal degradation, the latter dependent on PKCα. We find that one function of RA in regulating vascular WNT signaling is to modulate the pericyte numbers in the developing brain vasculature. RA-mediated regulation of vascular WNT signaling could be needed to prevent over-recruitment of pericytes that might impair endothelial-pericyte interactions crucial for vascular stability.

Pericyte

10.3389/fncel.2018.00476

Cite

Citations (23)

Foxc1 is required by pericytes during fetal brain angiogenesis

Biology Open (2013)

Julie A. Siegenthaler Youngshik Choe Katelin P. Patterson Ivy Hsieh Dan Li

Summary Brain pericytes play a critical role in blood vessel stability and blood–brain barrier maturation. Despite this, how brain pericytes function in these different capacities is only beginning to be understood. Here we show that the forkhead transcription factor Foxc1 is expressed by brain pericytes during development and is critical for pericyte regulation of vascular development in the fetal brain. Conditional deletion of Foxc1 from pericytes and vascular smooth muscle cells leads to late-gestation cerebral micro-hemorrhages as well as pericyte and endothelial cell hyperplasia due to increased proliferation of both cell types. Conditional Foxc1 mutants do not have widespread defects in BBB maturation, though focal breakdown of BBB integrity is observed in large, dysplastic vessels. qPCR profiling of brain microvessels isolated from conditional mutants showed alterations in pericyte-expressed proteoglycans while other genes previously implicated in pericyte–endothelial cell interactions were unchanged. Collectively these data point towards an important role for Foxc1 in certain brain pericyte functions (e.g. vessel morphogenesis) but not others (e.g. barriergenesis).

Pericyte

Cell type

Mural cell

Conditional gene knockout

10.1242/bio.20135009

Cite

Citations (69)

[P1.37]: Tangential migration defects in a mouse mutant for foxc1 recovered in a genetic screen

International Journal of Developmental Neuroscience (2008)

Konstantinos Zarbalis Yun Jeong Choe Julie A. Siegenthaler Jacqueline T. Hecht Samuel J. Pleasure

10.1016/j.ijdevneu.2008.09.087

Cite

Citations (0)

‘Formation and function of the meninges arachnoid barrier around the developing brain’

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Julia Derk Christina N. Como Hannah E. Jones Luke R. Joyce Stephanie Bonney

Abstract Barriers at the level of the brain endothelium, choroid plexus, and meninges strictly regulate movement of molecules and cells into and out of the central nervous system (CNS). In contrast to the blood-brain barrier and choroid plexus epithelial barrier, developmental timing and function of the meningeal arachnoid barrier, a layer of epithelial-like cells connected by tight and adherens junctions, is largely unknown. To begin to address this, we mined our E14.5 mouse single cell transcriptomic (scRNA-seq) meningeal fibroblast data set and identified the repression of Wnt-β-catenin signaling as a key mechanism underlying the specification of epithelial-like arachnoid barrier cells from Collagen 1+ and Crabp2+ mesenchymal meningeal precursors. We show that elevating Wnt-β-catenin signaling in prenatal meningeal mesenchymal cells prevented the development of arachnoid barrier cells. In the absence of dorsal arachnoid barrier cells, the prenatal meninges and brain are penetrable to biocytin-TMR and Streptococcus agalactiae (Group B Streptococcus , GBS), the leading pathogen known to drive life-threatening neonatal meningitis. We show that a layer of Claudin 11 (tight junction) and E-cadherin (adherens junction) expressing arachnoid barrier cells appear around the mouse brain from E13-E15 and the emergence of a functional barrier by E17 coincides with junctional localization of Claudin 11. Postnatal growth of the arachnoid barrier is marked initially by proliferation and later re-organization of junctional domains. This work provides fundamental knowledge on development and prenatal function of a meningeal arachnoid barrier, and novel tools for future studies on regional functions of this CNS barrier in the meninges.

Adherens junction

Meninges

Barrier function

10.1101/2022.06.10.495709

Cite

Citations (5)

ETHANOL INDUCES HETEROTOPIAS IN ORGANOTYPIC CULTURES OF RAT CEREBRAL CORTEX.

Alcoholism Clinical and Experimental Research (2004)

Sandra M. Mooney Julie A. Siegenthaler Michael W. Miller

Abnormalities in the migration of cortical neurons to ectopic sites can be caused by prenatal exposure to ethanol. In extreme cases, cells migrate past the pial surface and form suprapial heterotopias or ‘warts’. We used organotypic slice cultures from 17-day-old rat fetuses to examine structural and molecular changes that accompany wart formation. Cultures were exposed to ethanol (0, 200, 400 or 800 mg/dl) and maintained for 2–32 h. Fixed slices were sectioned and immunolabeled with antibodies directed against calretinin, reelin, nestin, GFAP, doublecortin, MAP-2 and NeuN. Ethanol promoted the widespread infiltration of the marginal zone (MZ) with neurons and the focal formation of warts. The appearance of warts is time- and concentration-dependent. Heterotopias comprised migrating neurons and were not detected in control slices. Warts were associated with breaches in the array of Cajal–Retzius cells and with translocation of reelin-immunoexpression from the MZ to the outer limit of the wart. Ethanol also altered the morphology of the radial glia. Thus, damage to the integrity of superficial cortex allows neurons to infiltrate the MZ, and if the pial–subpial glial barrier is also compromised these ectopic neurons can move beyond the normal cerebral limit to form a wart.

10.1097/00000374-200408002-00125

Cite

Citations (0)

Revisiting the nutritional risk screening (NRS) score: need for adaptation to predict treatment response. a secondary analysis of a randomized controlled trial

Clinical Nutrition ESPEN (2023)

Carla Wunderle Julie A. Siegenthaler David S. Seres Philipp Schüetz

10.1016/j.clnesp.2023.09.684

Cite

Citations (0)

Retinoic acid signaling in mouse retina endothelial cells is required for early angiogenic growth

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Christina N. Como Cesar Cervantes Bradley Pawlikowski Julie A. Siegenthaler

ABSTRACT The development of the retinal vasculature is essential to maintain health of the tissue, but the developmental mechanisms are not completely understood. The aim of this study was to investigate the cell-autonomous role of retinoic acid signaling in endothelial cells during retina vascular development. Using a temporal and cell-specific mouse model to disrupt retinoic acid signaling in endothelial cells in the postnatal retina ( Pdgfb icre/+ dnRAR403 fl/fl mutants), we discovered that angiogenesis in the retina is significantly decreased with a reduction in retina vascularization, endothelial tip cell number and filipodia, and endothelial ‘crowding’ of stalk cells. Interestingly, by P15, the vasculature can overcome the early angiogenic defect and fully vascularized the retina. At P60, the vasculature is intact with no evidence of retina cell death or altered blood retinal barrier integrity. Further, we identified that the angiogenic defect seen in mutants at P6 correlates with decreased Vegfr3 expression in endothelial cells. Collectively, our work identified a previously unappreciated function for endothelial retinoic acid signaling in early retinal angiogenesis.

10.1101/2022.05.09.491241

Cite

Citations (0)