Postnatal subventricular zone (SVZ) neural stem cells generate forebrain glia, namely
astrocytes and oligodendrocytes. The cues necessary for this process are unclear,
despite this phase of brain development being pivotal in forebrain gliogenesis. Galectin-3
(Gal-3) is increased in multiple brain pathologies and thereby regulates astrocyte
proliferation and inflammation in injury. To study the function of Gal-3 in inflammation
and gliogenesis, we carried out functional studies in mouse. We overexpressed Gal-3
with electroporation and using immunohistochemistry surprisingly found no inflammation
in the healthy postnatal SVZ. This allowed investigation of inflammation-independent
effects of Gal-3 on gliogenesis. Loss of Gal-3 function via knockdown or conditional
knockout reduced gliogenesis, whereas Gal-3 overexpression increased it. Gal-3 overexpression
also increased the percentage of striatal astrocytes generated by the SVZ but decreased
the percentage of oligodendrocytes. These novel findings were further elaborated with
multiple analyses demonstrating that Gal-3 binds to the bone morphogenetic protein
receptor one alpha (BMPR1α) and increases bone morphogenetic protein (BMP) signaling.
Conditional knockout of BMPR1α abolished the effect of Gal-3 overexpression on gliogenesis.
Gain-of-function of Gal-3 is relevant in pathological conditions involving the human
forebrain, which is particularly vulnerable to hypoxia/ischemia during perinatal gliogenesis.
Hypoxic/ischemic injury induces astrogliosis, inflammation and cell death. We show
that Gal-3 immunoreactivity was increased in the perinatal human SVZ and striatum
after hypoxia/ischemia. Our findings thus show a novel inflammation-independent function
for Gal-3; it is necessary for gliogenesis and when increased in expression can induce
astrogenesis via BMP signaling.
