Molecular mechanisms of tubulogenesis revealed in the sea star hydro-vascular organ
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Abstract
A fundamental goal in the organogenesis field is to understand how cells organize into tubular shapes. Toward this aim, we have established the hydro-vascular organ in the sea star Patiria miniata as a model for tubulogenesis. In this animal, bilateral tubes grow out from the tip of the developing gut, and precisely extend to specific sites in the larva. This growth involves cell migration coupled with mitosis in distinct zones. Cell proliferation requires FGF signaling, whereas the three-dimensional orientation of the organ depends on Wnt signaling. Specification and maintenance of tube cell fate requires Delta/Notch signaling. Moreover, we identify target genes of the FGF pathway that contribute to tube morphology, revealing molecular mechanisms for tube outgrowth. Finally, we report that FGF activates the Six1/2 transcription factor, which serves as an evolutionarily ancient regulator of branching morphogenesis. This study uncovers distinct mechanisms of tubulogenesis in vivo and we propose that cellular dynamics in the sea star hydro-vascular organ represents a key comparison for understanding the evolution of vertebrate organs.
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Cell proliferation requires FGF signaling, whereas the three-dimensional orientation of the organ depends on Wnt signaling. Specification and maintenance of tube cell fate requires Delta/Notch signaling.
Consider putting these in the order you reported them in the results (like my suggestion for the highlights below)
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❖ The Wnt pathway controls directional outgrowth❖ The FGF pathway promotes regionalized cell proliferation❖ The Notch/Delta pathway is essential in cell fate repression in tubulogenesis
I would consider re-ordering these to mirror the order you present them in the results - Notch/Delta --> Wnt --> FGF --> FGF targets
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Although the basal lamina was generally contiguous with the tube epithelium, we observed a laminin protrusion on the anterior side of the tube that was devoid of cells (Figure 1 E, F arrows), suggesting that cells left the laminin network on the anterior side after their migration toward the posterior end.
I am so fascinated by this - did you see cells help make this protrusion and then leave? What is doing this if the region is acellular? And is there a L/R bias like it looks like in Fig. 1E?
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We found that in Wnt-inhibited larvae, the tubes elongated towards the dorsal ectoderm instead of posteriorly, as in controls
Any clue why in the absence of Wnt the tube still has an orientation (dorsal) but just to the wrong place rather than just a random orientation? Is there some signal that in the absence of Wnt that draws the tube dorsal (Nodal/BMP or something like this?)
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To define the nature of sea star tube formation, we took advantage of the optical clarity of the larvae and developed techniques to immobilize and live image morphogenesis continuously from gastrulation to early larval stages (Figure 1- Video 1)
this is SO amazing! Have you considered writing up a protocol for protocols.io or something similar to highlight how cool this is!
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Since the hydropore canal forms by tissue bending at a defined branch point, we propose that Six1/2 activation downstream of FGF signaling is critical for branching morphogenesis.
woah! I wonder if it's sufficient to induce extra branching morphogenesis if you OE it spatially/temporally??? (not for this paper - there's so much amazing biology in this paper… do this in your own lab! :). )
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These results suggest that continued Delta/Notch signaling is important to restrict excess muscle specification.
this is really really interesting - and would be fascinating to follow up on as a model for transdifferentiation!
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Since the hydropore canal forms by tissue bending at a defined branch point, we propose that Six1/2 activation downstream of FGF signaling is critical for branching morphogenesis.
woah! I wonder if it's sufficient to induce extra branching morphogenesis if you OE it spatially/temporally??? (not for this paper - there's so much amazing biology in this paper… do this in your own lab! :). )
-
We found that in Wnt-inhibited larvae, the tubes elongated towards the dorsal ectoderm instead of posteriorly, as in controls
Any clue why in the absence of Wnt the tube still has an orientation (dorsal) but just to the wrong place rather than just a random orientation? Is there some signal that in the absence of Wnt that draws the tube dorsal (Nodal/BMP or something like this?)
-
These results suggest that continued Delta/Notch signaling is important to restrict excess muscle specification.
this is really really interesting - and would be fascinating to follow up on as a model for transdifferentiation!
-
Although the basal lamina was generally contiguous with the tube epithelium, we observed a laminin protrusion on the anterior side of the tube that was devoid of cells (Figure 1 E, F arrows), suggesting that cells left the laminin network on the anterior side after their migration toward the posterior end.
I am so fascinated by this - did you see cells help make this protrusion and then leave? What is doing this if the region is acellular? And is there a L/R bias like it looks like in Fig. 1E?
-
To define the nature of sea star tube formation, we took advantage of the optical clarity of the larvae and developed techniques to immobilize and live image morphogenesis continuously from gastrulation to early larval stages (Figure 1- Video 1)
this is SO amazing! Have you considered writing up a protocol for protocols.io or something similar to highlight how cool this is!
-
❖ The Wnt pathway controls directional outgrowth❖ The FGF pathway promotes regionalized cell proliferation❖ The Notch/Delta pathway is essential in cell fate repression in tubulogenesis
I would consider re-ordering these to mirror the order you present them in the results - Notch/Delta --> Wnt --> FGF --> FGF targets
-
Cell proliferation requires FGF signaling, whereas the three-dimensional orientation of the organ depends on Wnt signaling. Specification and maintenance of tube cell fate requires Delta/Notch signaling.
Consider putting these in the order you reported them in the results (like my suggestion for the highlights below)
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