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Journal of Neuroscience, Vol 14, 5725-5740, Copyright © 1994 by Society for Neuroscience
Otx1 and Otx2 define layers and regions in developing cerebral cortex and cerebellum
GD Frantz, JM Weimann, ME Levin and SK McConnell
Department of Biological Sciences, Stanford University, California 94305.
Within the cerebral and cerebellar cortices, neurons are organized in
layers that segregate neurons with distinctive morphologies and axonal
connections, and areas or regions that correspond to distinct functional
domains. To explore the molecular underpinnings of pattern formation in
layered regions of the CNS, we have characterized the patterns of
expression of two homeodomain genes, Otx1 and Otx2, by in situ
hybridization during embryonic and postnatal development in the rat. Otx1
and Otx2 are vertebrate homologs of the Drosophila gap gene orthodenticle,
and are expressed during the development of the murine CNS (Simeone et al.,
1992). Here we report that Otx1 mRNA is expressed in a subpopulation of
neurons within cortical layers 5 and 6 during postnatal and adult life.
This gene is also expressed by the precursors of deep-layer neurons within
the developing cerebral ventricular zone, but is apparently downregulated
by the progenitors of upper-layer neurons; Otx1 is never expressed by the
neurons of layers 1-4. The spatial and temporal patterns suggest that Otx1
may play a role in the specification or differentiation of neurons in the
deep layers of the cerebral cortex. Within the cerebellum, mRNAs for Otx1
and Otx2 are found within the external granular layer (EGL), but in three
spatially distinct domains. During postnatal development, Otx1 is expressed
within anterior cerebellar lobules; Otx2 mRNA is localized posteriorly, and
a region of overlap in mid-cerebellum defines a third domain in which both
genes are expressed. The boundaries of Otx1 and Otx2 expression correspond
to the major functional boundaries of the cerebellum, and define the
vestibulocerebellum, spinocerebellum, and pontocerebellum, respectively.
Spatially restricted patterns of hybridization are observed early in
postnatal life, at times that correspond roughly to the invasion of spinal
and pontine afferents into the cerebellum (Arsenio-Nunes and Sotelo, 1985;
Mason, 1987). These results raise the possibility that Otx1 and Otx2 play a
role in cerebellar regionalization during early development.
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