Mnb/Dyrk1A Is Transiently Expressed and Asymmetrically Segregated in Neural Progenitor Cells at the Transition to Neurogenic Divisions

Abstract

The Minibrain (Mnb) gene encodes a new family of protein kinases that is evolutionarily conserved from insects to humans. In Drosophila, Mnb is involved in postembryonic neurogenesis. In humans, MNB has been mapped within the Down's Syndrome (DS) critical region of chromosome 21 and is overexpressed in DS embryonic brain. In order to study a possible role of Mnb on the neurogenesis of vertebrate brain, we have cloned the chick Mnb orthologue and studied the spatiotemporal expression of Mnb in proliferative regions of the nervous system. In early embryos, Mnb is expressed before the onset of neurogenesis in the three general locations where neuronal precursors are originated: neuroepithelia of the neural tube, neural crest, and cranial placodes. Mnb is transiently expressed during a single cell cycle of neuroepithelial progenitor (NEP) cells. Mnb expression precedes and widely overlaps with the expression of Tis21, an antiproliferative gene that has been reported to be expressed in the onset of neurogenic divisions of NEP cells. Mnb transcription begins in mitosis, continues during G1, and stops before S-phase. Very interestingly, we have found that Mnb mRNA is asymmetrically localized during the mitosis of these cells and inherited by one of the sibling cells after division. We propose that Mnb defines a transition step between proliferating and neurogenic divisions of NEP cells.