Limits...
Development-on-chip: in vitro neural tube patterning with a microfluidic device.

Demers CJ, Soundararajan P, Chennampally P, Cox GA, Briscoe J, Collins SD, Smith RL - Development (2016)

Bottom Line: Currently, in vivo and ex vivo studies of these signaling factors present some inherent ambiguity.In this article, we present a versatile microfluidic platform capable of mimicking the spatial and temporal chemical environments found in vivo during neural tube development.Simultaneous opposing and/or orthogonal gradients of developmental morphogens can be maintained, resulting in neural tube patterning analogous to that observed in vivo.

View Article: PubMed Central - PubMed

Affiliation: Microinstruments and Systems Laboratory, University of Maine, Orono, ME 04469, USA Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.

No MeSH data available.


Related in: MedlinePlus

Graphical overview of the microfluidic reconstruction of the neural tube. (A,B) Schematic of a neural tube highlighting the 100 µm ‘slice’ recreated by the microfluidic device. Four primary signals (RA, SHH, BMP and FGF) are responsible for patterning the bulk of the neural tube (NC, notochord) (A). The SHH gradient, which is responsible for directing the differentiation of ventral neural progenitors into discrete domains of neurons, is recreated inside the cell culture chamber of the microdevice (B). Flow channels running under the cell chamber supply nutrients as well as desired guidance molecules to the cells in the culture chamber. Morphogen concentration gradients are established across the chamber using the vias in a standard source/sink configuration with the walls of the chamber acting as reflective boundaries. (C) A top (rotated) view of B, as seen through the cover glass. (D) A photograph of the microdevice sitting on top of a dime indicates the scale of the device. FP, floor plate; RP, roof plate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4920155&req=5

DEV126847F1: Graphical overview of the microfluidic reconstruction of the neural tube. (A,B) Schematic of a neural tube highlighting the 100 µm ‘slice’ recreated by the microfluidic device. Four primary signals (RA, SHH, BMP and FGF) are responsible for patterning the bulk of the neural tube (NC, notochord) (A). The SHH gradient, which is responsible for directing the differentiation of ventral neural progenitors into discrete domains of neurons, is recreated inside the cell culture chamber of the microdevice (B). Flow channels running under the cell chamber supply nutrients as well as desired guidance molecules to the cells in the culture chamber. Morphogen concentration gradients are established across the chamber using the vias in a standard source/sink configuration with the walls of the chamber acting as reflective boundaries. (C) A top (rotated) view of B, as seen through the cover glass. (D) A photograph of the microdevice sitting on top of a dime indicates the scale of the device. FP, floor plate; RP, roof plate.

Mentions: During spinal cord development, organizing centers surrounding the neural tube, such as the notochord, paraxial mesoderm and roof/floor plates, release chemical cues directing neural precursor cells to differentiate into mature neurons (Fig. 1). The most studied of these cues is sonic hedgehog (SHH), which is generated in notochord and floor plate cells establishing a ventral (high) to dorsal (low) concentration gradient across the neural tube (Ribes and Briscoe, 2009) directing the differentiation of ventral neural progenitors (Roelink et al., 1995) into highly organized domains of neural subtypes (Bushati and Briscoe, 1994). An opposing gradient of bone morphogenetic protein (BMP) and other members of the transforming growth factor beta (TGFβ) superfamily of signaling molecules are simultaneously released by roof plate cells, concurrently patterning the dorsal half of the neural tube and establishing a cross-repressive boundary between the dorsal and ventral halves of the developing spinal cord (Le Dréau et al., 2012). Patterning along the anteroposterior (AP) axis occurs simultaneously with dorsoventral (DV) patterning and is the result of opposing gradients of retinoic acid (RA) and fibroblast growth factor (FGF)/WNT, which induce a sequential activation of homeobox (Hox) genes (Diez del Corral et al., 2003; Liu et al., 2001). Current models indicate that these four signaling molecules (SHH, BMP, RA and FGF) jointly coordinate most of the spatial and temporal differentiation of the neural tube (Wilson and Maden, 2005).


Development-on-chip: in vitro neural tube patterning with a microfluidic device.

Demers CJ, Soundararajan P, Chennampally P, Cox GA, Briscoe J, Collins SD, Smith RL - Development (2016)

Graphical overview of the microfluidic reconstruction of the neural tube. (A,B) Schematic of a neural tube highlighting the 100 µm ‘slice’ recreated by the microfluidic device. Four primary signals (RA, SHH, BMP and FGF) are responsible for patterning the bulk of the neural tube (NC, notochord) (A). The SHH gradient, which is responsible for directing the differentiation of ventral neural progenitors into discrete domains of neurons, is recreated inside the cell culture chamber of the microdevice (B). Flow channels running under the cell chamber supply nutrients as well as desired guidance molecules to the cells in the culture chamber. Morphogen concentration gradients are established across the chamber using the vias in a standard source/sink configuration with the walls of the chamber acting as reflective boundaries. (C) A top (rotated) view of B, as seen through the cover glass. (D) A photograph of the microdevice sitting on top of a dime indicates the scale of the device. FP, floor plate; RP, roof plate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920155&req=5

DEV126847F1: Graphical overview of the microfluidic reconstruction of the neural tube. (A,B) Schematic of a neural tube highlighting the 100 µm ‘slice’ recreated by the microfluidic device. Four primary signals (RA, SHH, BMP and FGF) are responsible for patterning the bulk of the neural tube (NC, notochord) (A). The SHH gradient, which is responsible for directing the differentiation of ventral neural progenitors into discrete domains of neurons, is recreated inside the cell culture chamber of the microdevice (B). Flow channels running under the cell chamber supply nutrients as well as desired guidance molecules to the cells in the culture chamber. Morphogen concentration gradients are established across the chamber using the vias in a standard source/sink configuration with the walls of the chamber acting as reflective boundaries. (C) A top (rotated) view of B, as seen through the cover glass. (D) A photograph of the microdevice sitting on top of a dime indicates the scale of the device. FP, floor plate; RP, roof plate.
Mentions: During spinal cord development, organizing centers surrounding the neural tube, such as the notochord, paraxial mesoderm and roof/floor plates, release chemical cues directing neural precursor cells to differentiate into mature neurons (Fig. 1). The most studied of these cues is sonic hedgehog (SHH), which is generated in notochord and floor plate cells establishing a ventral (high) to dorsal (low) concentration gradient across the neural tube (Ribes and Briscoe, 2009) directing the differentiation of ventral neural progenitors (Roelink et al., 1995) into highly organized domains of neural subtypes (Bushati and Briscoe, 1994). An opposing gradient of bone morphogenetic protein (BMP) and other members of the transforming growth factor beta (TGFβ) superfamily of signaling molecules are simultaneously released by roof plate cells, concurrently patterning the dorsal half of the neural tube and establishing a cross-repressive boundary between the dorsal and ventral halves of the developing spinal cord (Le Dréau et al., 2012). Patterning along the anteroposterior (AP) axis occurs simultaneously with dorsoventral (DV) patterning and is the result of opposing gradients of retinoic acid (RA) and fibroblast growth factor (FGF)/WNT, which induce a sequential activation of homeobox (Hox) genes (Diez del Corral et al., 2003; Liu et al., 2001). Current models indicate that these four signaling molecules (SHH, BMP, RA and FGF) jointly coordinate most of the spatial and temporal differentiation of the neural tube (Wilson and Maden, 2005).

Bottom Line: Currently, in vivo and ex vivo studies of these signaling factors present some inherent ambiguity.In this article, we present a versatile microfluidic platform capable of mimicking the spatial and temporal chemical environments found in vivo during neural tube development.Simultaneous opposing and/or orthogonal gradients of developmental morphogens can be maintained, resulting in neural tube patterning analogous to that observed in vivo.

View Article: PubMed Central - PubMed

Affiliation: Microinstruments and Systems Laboratory, University of Maine, Orono, ME 04469, USA Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.

No MeSH data available.


Related in: MedlinePlus