Absence of the transcription factor Nfib delays the formation of the basilar pontine and other mossy fiber nuclei.
Transcription factors of the Nuclear Factor I (Nfi) family are important for the development of specific neuronal and glial populations in the nervous system. One such population, the neurons of the basilar pontine nuclei, expresses high levels of Nfi proteins, and the pontine nuclei are greatly reduced in mice lacking a functional Nfib gene. Pontine neurons, along with other precerebellar neurons that populate the hindbrain, arise from precursors in the lower rhombic lip and migrate anteroventrally to reach their final location. Using immunohistochemistry, we find that NFI-B expression is specific for mossy fiber populations of the precerebellar system. Analysis of the Nfib(-/-) hindbrain indicates that the development of the basilar pontine nuclei is delayed, with pontine neurons migrating 1-2 days later than in control animals, and that significantly fewer pontine neurons are produced. While the mossy fiber nuclei of the caudal medulla do form, they also exhibit a developmental delay. Nfia and Nfix null mice exhibit no apparent pontine phenotype, implying specificity in the action of NFI family members. Collectively, these data demonstrate that Nfib plays an important role in the generation of precerebellar mossy fiber neurons, and may do so at least in part by regulating neurogenesis.
Kumbasar
Asli
A
Department of Anatomy and Neurobiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Plachez
Céline
C
Gronostajski
Richard M
RM
Richards
Linda J
LJ
Litwack
E David
ED
D000818:Animals; D002525:Cerebellar Cortex / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011149:Pons / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism
D005136:Eye Proteins; D018398:Homeodomain Proteins; D051839:NFI Transcription Factors; C497646:Nfia protein, mouse; C484683:Nfib protein, mouse; C497650:Nfix protein, mouse; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins