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The Journal of Neuroscience, June 22, 2005, 25(25):5857-5865; doi:10.1523/JNEUROSCI.4621-04.2005
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Development/Plasticity/Repair
Mash1 and Math3 Are Required for Development of Branchiomotor Neurons and Maintenance of Neural Progenitors
Ryosuke Ohsawa, Toshiyuki Ohtsuka, andRyoichiro Kageyama Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
Basic helix-loop-helix (bHLH) transcription factors are known to play important roles in neuronal determination and differentiation. However, their exact roles in neural development still remain to be determined because of the functional redundancy. Here, we examined the roles of neural bHLH genes Mash1 and Math3 in the development of trigeminal and facial branchiomotor neurons, which derive from rhombomeres 2-4. In Math3-null mutant mice, facial branchiomotor neurons are misspecified, and both trigeminal and facial branchiomotor neurons adopt abnormal migratory pathways. In Mash1;Math3 double-mutant mice, trigeminal and facial branchiomotor neurons are severely reduced in number partly because of increased apoptosis. In addition, neurons with migratory defects are intermingled over the midline from either side of the neural tube. Furthermore, oligodendrocyte progenitors of rhombomere 4 are reduced in number. In the absence of Mash1 and Math3, expression of Notch signaling components is severely downregulated in rhombomere 4 and neural progenitors are not properly maintained, which may lead to intermingling of neurons and a decrease in oligodendrocyte progenitors. These results indicate that Mash1 and Math3 not only promote branchiomotor neuron development but also regulate the subsequent oligodendrocyte development and the cytoarchitecture by maintaining neural progenitors through Notch signaling.
Key words: bHLH; branchiomotor neuron; facial nucleus; hindbrain; Notch signaling; trigeminal nucleus
Received Nov 10, 2004; revised April 11, 2005; accepted May 6, 2005.
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