Mash1 and Math3 are required for development of branchiomotor neurons and maintenance of neural progenitors.
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.
Ohsawa
Ryosuke
R
Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Ohtsuka
Toshiyuki
T
Kageyama
Ryoichiro
R
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D017931:DNA Primers; D047108:Embryonic Development / Q000235:genetics; D005154:Facial Nerve / Q000002:abnormalities* / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D014276:Trigeminal Nerve / Q000002:abnormalities* / Q000196:embryology
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D009419:Nerve Tissue Proteins; C499317:Ascl1 protein, mouse; C104516:Neurod4 protein, mouse