Fractones and basement membranes: matrix for patterning, growth and development

Abstract

More and more evidence supports the view that extracellular matrix (ECM) is essential for growth and patterning during development. However, the mechanisms underlying patterning and morphogenesis are unknown. In both adult and developing mammalians, we have characterized a new type of extracellular matrix structure that we have named fractones. Fractones are chemically similar to basement membranes but differ from the latter by their location. Fractones reside in the parenchyma of tissues and organs. They are are visualized as particles by light microscopy but often display a fractal ultrastructure. In contrast, basement membranes are located as sheaths at the connective tissue/parenchyma interface. We have shown that fractone‐associated heparan sulfates bind and activate growth factors to regulate stem cell proliferation in the neurogenic zone of the adult brain. Here, we used multiple fluorescence immunohistochemistry to visualize fractones, basement membranes and cell proliferation throughout mouse development, with a focus on brain structuration. Fractones preceded basement membranes and were associated with proliferating pluripotent stem cells in the inner cell mass of the blastocyst. During gastrulation, fractones were found in the three germinal tissues. During neurulation, fractones were visualized at the vicinity of proliferating neuroepithelial cells in the notoplate and in the ventricular zone. During corticalization, fractones gradually displaced through the neural tissue according to an in‐out gradient towards the basement membrane of superficial meninges. At this time, fractone distribution negatively correlated with neural cell proliferation. For white matter tract formation, axonal growth was accompanied by fractones along meningeal elongations that progressively patterned the forming brain. Then, brain fractones disappeared only to reappear soon after birth throughout the sub ventricular zone, a location that persisted into adulthood. Together, our results strongly suggest that fractones and basement membranes are essential for patterning and morphogenesis.Support or Funding InformationSupported by JSPS S09109This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.