<it>Neurog1</it> and <it>Neurog2</it> coordinately regulate development of the olfactory system

• Main Authors: Shaker Tarek, Dennis Daniel, Kurrasch Deborah M, Schuurmans Carol
• Format: Article
• Language: English
• Published: BMC 2012-08-01
• Series: Neural Development
• Subjects: Olfactory bulb; Olfactory epithelium; Proneural genes; Neuronal fate specification; Neuronal migration; Axonal innervation
• Online Access: http://www.neuraldevelopment.com/content/7/1/28

<p>Abstract</p> <p>Background</p> <p>Proneural genes encode basic helix–loop–helix transcription factors that specify distinct neuronal identities in different regions of the nervous system. In the embryonic telencephalon, the proneural genes <it>Neurog1</it> and <it>Neurog2</it> specify a dorsal regional identity and glutamatergic projection neuron phenotype in the presumptive neocortex, but their roles in cell fate specification in the olfactory bulb, which is also partly derived from dorsal telencephalic progenitors, have yet to be assessed. Given that olfactory bulb development is guided by interactions with the olfactory epithelium in the periphery, where proneural genes are also expressed, we investigated the roles of <it>Neurog1</it> and <it>Neurog2</it> in the coordinated development of these two olfactory structures.</p> <p>Results</p> <p><it>Neurog1/2</it> are co-expressed in olfactory bulb progenitors, while only <it>Neurog1</it> is widely expressed in progenitors for olfactory sensory neurons in the olfactory epithelium. Strikingly, only a remnant of an olfactory bulb forms in <it>Neurog1</it>^−/−<it>;Neurog2</it>^−/− double mutants, while this structure is smaller but distinguishable in <it>Neurog1</it>^−/− single mutants and morphologically normal in <it>Neurog2</it>^{<it>−/−</it>} single mutants. At the cellular level, fewer glutamatergic mitral and juxtaglomerular cells differentiate in <it>Neurog1</it>^−/−<it>;Neurog2</it>^−/− double-mutant olfactory bulbs. Instead, ectopic olfactory bulb interneurons are derived from dorsal telencephalic lineages in <it>Neurog1</it>^−/−<it>;Neurog2</it>^−/− double mutants and to a lesser extent in <it>Neurog2</it>^{<it>−/−</it>} single mutants. Conversely, cell fate specification is normal in <it>Neurog1</it>^{<it>−/−</it>} olfactory bulbs, but aberrant patterns of cell proliferation and neuronal migration are observed in <it>Neurog1</it>^{<it>−/−</it>} single and <it>Neurog1</it>^−/−<it>;Neurog2</it>^−/− double mutants, probably contributing to their altered morphologies. Finally, in <it>Neurog1</it>^{<it>−/−</it>} and <it>Neurog1</it>^−/−<it>;Neurog2</it>^−/− embryos, olfactory sensory neurons in the epithelium, which normally project to the olfactory bulb to guide its morphogenesis, fail to innervate the olfactory bulb.</p> <p>Conclusions</p> <p>We have identified a cell autonomous role for <it>Neurog1/</it>2 in specifying the glutamatergic identity of olfactory bulb neurons. Furthermore, <it>Neurog1</it> (and not <it>Neurog2</it>) is required to guide olfactory sensory neuron innervation of the olfactory bulb, the loss of which results in defects in olfactory bulb proliferation and tissue morphogenesis. We thus conclude that <it>Neurog1/2</it> together coordinate development of the olfactory system, which depends on tissue interactions between the olfactory bulb and epithelium.</p>