ABSTRACT
INSM1 is a zinc-finger protein expressed in the developing nervous system and pancreas as well as in medulloblastomas and neuroendocrine tumors. With in situ hybridization combined with immunohistochemistry, we detected INSM1 mRNA in all embryonic to adult neuroproliferative areas examined: embryonic neocortex, ganglionic eminence, midbrain, retina, hindbrain, and spinal cord; autonomic, dorsal root, trigeminal and spiral ganglia; olfactory and vomeronasal organ epithelia; postnatal cerebellum; and juvenile to adult subgranular zone of dentate gyrus, subventricular zone, and rostral migratory stream leading to olfactory bulb. In most of these neurogenic areas, subsets of neuronal progenitors and nascent, but not mature, neurons express INSM1. For example, in developing cerebellum, INSM1 is present in proliferating progenitors of the outer external granule layer (EGL) and in postmitotic cells of the inner EGL, but not in mature granule cell neurons. Also, lining the neural tube from spinal cord to neocortex in mouse as well as human embryos, cells undergoing mitosis apically do not express INSM1. By contrast, nonsurface progenitors located in the basal ventricular and/or subventricular zones express INSM1. Whereas apical progenitors are proliferative and generate one or two additional progenitors, basal progenitors are thought to divide terminally and symmetrically to produce two neurons. The nematode ortholog of INSM1, EGL-46, is expressed during terminal symmetric neurogenic divisions and regulates the termination of proliferation. We propose that, in mice and humans, INSM1 is likewise expressed transiently during terminal neurogenic divisions, from late progenitors to nascent neurons, and particularly during symmetric neuronogenic divisions.