Molecular mechanisms of tubulogenesis revealed in the sea star hydro-vascular organ

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 requires 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 novel 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. Highlights The hydro-vascular organ of the sea star presents a valuable model of tubulogenesis In this organ tube extension is driven by cell migration coupled with cell proliferation at specific growth zones 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 A screen of FGF function revealed essential target gene expression, including the transcription factor Six1/2 Within a sister group to chordates, the sea star will reveal ancient mechanisms of tubulogenesis