ABSTRACT
Cells of the subplate (SP) and deep cortical plate (CP) are among the pioneer neurons of the developing cerebral cortex, an important group of early-born cells that impact cortical organization and function. Similarities between pioneer neurons in different cortical positions and heterogeneities in pioneer cells in the same cortical location, however, have made it difficult to appreciate the characteristics and functions of particular sets of these cells. Here, we provide a tool to illuminate a unique subset of SP and deep CP neurons: expression of a Tbrain-1 (Tbr1)-driven transgene. Transgene-expressing cells were consistently positive for neuronal but not glial markers, were born early in corticogenesis, representing just a subset of SP and deep CP neurons, were morphologically complex during the formation of the cortex, and were maintained into maturity. This analysis reveals a novel group of pioneer neurons and demonstrates unrecognized diversity within this cortical population. In the future, this information will help to uncover the roles of discrete pioneer populations in cortical development.
Subject(s)
Cell Differentiation/physiology , Cerebral Cortex/cytology , DNA-Binding Proteins/genetics , Animals , Animals, Newborn , Base Sequence , Biomarkers/metabolism , Cell Lineage/physiology , Cell Movement/physiology , Cell Proliferation , Cells, Cultured , Cerebral Cortex/embryology , Cerebral Cortex/growth & development , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Developmental/physiology , Green Fluorescent Proteins , Mice , Mice, Transgenic , Molecular Sequence Data , Nerve Tissue Proteins/metabolism , Neurons , RNA, Messenger , Stem Cells/cytology , T-Box Domain Proteins , Transgenes/physiologyABSTRACT
Cells of the subplate (SP) and deep cortical plate (CP) are among the pioneer neurons of the developing cerebral cortex, an important group of early-born cells that impact cortical organization and function. Similarities between pioneer neurons in different cortical positions and heterogeneities in pioneer cells in the same cortical location, however, have made it difficult to appreciate the characteristics and functions of particular sets of these cells. Here, we provide a tool to illuminate a unique subset of SP and deep CP neurons: expression of a Tbrain-1 (Tbr1)-driven transgene. Transgene-expressing cells were consistently positive for neuronal but not glial markers, were born early in corticogenesis, representing just a subset of SP and deep CP neurons, were morphologically complex during the formation of the cortex, and were maintained into maturity. This analysis reveals a novel group of pioneer neurons and demonstrates unrecognized diversity within this cortical population. In the future, this information will help to uncover the roles of discrete pioneer populations in cortical development.
Subject(s)
Cell Differentiation/physiology , Cerebral Cortex/embryology , Cerebral Cortex/growth & development , DNA-Binding Proteins/genetics , Neurons/metabolism , Stem Cells/metabolism , Animals , Animals, Newborn , Base Sequence , Biomarkers/metabolism , Cell Lineage/physiology , Cell Movement/physiology , Cell Proliferation , Cerebral Cortex/cytology , Gene Expression Regulation, Developmental/physiology , Green Fluorescent Proteins , Mice , Molecular Sequence Data , Nerve Tissue Proteins/metabolism , Neurons/cytology , RNA, Messenger/metabolism , Stem Cells/cytology , T-Box Domain Proteins , Transgenes/physiologyABSTRACT
Parcellation of the mammalian cerebral cortex into distinct areas is essential for proper cortical function; however, the developmental program that results in the genesis of distinct areas is not fully understood. We examined the expression of members of the EphA family-the EphA receptor tyrosine kinases and the ephrin-A ligands-within the developing mouse cerebral cortex, with the aim of characterizing this component of the molecular landscape during cortical parcellation. We found that specific embryonic zones, such as the ventricular, subventricular, intermediate, subplate, and marginal zones, as well as the cortical plate, were positive for particular EphA genes early in corticogenesis (E12-E15). Along with this zone-selective expression, several genes (EphA3, EphA4, EphA5) were evenly expressed along the axes of the developing cortex, whereas one family member (EphA7) was expressed in a distinct anteroposterior pattern. Later in corticogenesis (E16-E18), other EphA family members became selectively expressed, but only within the cortical plate: EphA6 was present posteriorly, and ephrin-A5 was expressed within a middle region. At birth, patterning of EphA gene expression was striking. Thus, we found that the expression of a single EphA gene or a combination of family members can define distinct embryonic zones and anteroposterior regions of the neocortex during development. To examine whether cellular context affects the patterning of EphA expression, we examined gene expression in embryonic cortical cells grown in vitro, such that all cellular contacts are lacking, and in Mash-1 mutant mice, in which thalamocortical connections do not form. We found that the expression patterns of most EphA family members remained stable in these scenarios, whereas the pattern of ephrin-A5 was altered. Taken together, this work provides a comprehensive picture of EphA family expression during mouse corticogenesis and demonstrates that most EphA expression profiles are cell intrinsically based, whereas ephrin-A5 is plastically regulated.
