Finding a Role for Cajal-Retzius Cells in Cerebral Cortex Development

Thyroid hormones (TH, including the prohormone thyroxine (T4) and its active deiodinated derivative 3,,5-triiodo-L-thyronine (T3)) are important regulators of vertebrates neurodevelopment. Specific transporters and deiodinases are required to ensure T3 access to the developing brain. T3 activates a number of differentiation processes in neuronal and glial cell types by binding to nuclear receptors, acting directly on transcription. Only few T3 target genes are currently known. Deeper investigations are urgently needed, considering that some chemicals present in food are believed to interfere with T3 signaling with putative neurotoxic consequences.

Download Full-text

Disabled-1 acts downstream of Reelin in a signaling pathway that controls laminar organization in the mammalian brain

Development ◽

10.1242/dev.125.18.3719 ◽

1998 ◽

Vol 125 (18) ◽

pp. 3719-3729 ◽

Cited By ~ 2

Author(s):

D.S. Rice ◽

M. Sheldon ◽

G. D'Arcangelo ◽

K. Nakajima ◽

D. Goldowitz ◽

...

Keyword(s):

Cerebral Cortex ◽

Signaling Pathway ◽

Developmental Process ◽

Cortical Plate ◽

Mammalian Brain ◽

Granule Neurons ◽

Adapter Protein ◽

Cell Position ◽

Neuronal Precursors ◽

Retzius Cells

Mutation of either reelin (Reln) or disabled-1 (Dab1) results in widespread abnormalities in laminar structures throughout the brain and ataxia in reeler and scrambler mice. Both exhibit the same neuroanatomical defects, including cerebellar hypoplasia with Purkinje cell ectopia and disruption of neuronal layers in the cerebral cortex and hippocampus. Despite these phenotypic similarities, Reln and Dab1 have distinct molecular properties. Reln is a large extracellular protein secreted by Cajal-Retzius cells in the forebrain and by granule neurons in the cerebellum. In contrast, Dab1 is a cytoplasmic protein which has properties of an adapter protein that functions in phosphorylation-dependent intracellular signal transduction. Here, we show that Dab1 participates in the same developmental process as Reln. In scrambler mice, neuronal precursors are unable to invade the preplate of the cerebral cortex and consequently, they do not align within the cortical plate. During development, cells expressing Dab1 are located next to those secreting Reln at critical stages of formation of the cerebral cortex, cerebellum and hippocampus, before the first abnormalities in cell position become apparent in either reeler or scrambler. In reeler, the major populations of displaced neurons contain elevated levels of Dab1 protein, although they express normal levels of Dab1 mRNA. This suggests that Dab1 accumulates in the absence of a Reln-evoked signal. Taken together, these results indicate that Dab1 functions downstream of Reln in a signaling pathway that controls cell positioning in the developing brain.

Download Full-text

Single-cell transcriptomic analysis identifies neocortical developmental differences between human and mouse

10.1101/2020.04.23.056390 ◽

2020 ◽

Author(s):

Ziheng Zhou ◽

Shuguang Wang ◽

Dengwei Zhang ◽

Xiaosen Jiang ◽

Jie Li ◽

...

Keyword(s):

Cerebral Cortex ◽

Single Cell ◽

Developmental Trajectories ◽

Expression Patterns ◽

Development Stage ◽

Inhibitory Neurons ◽

Projection Neurons ◽

Cerebral Cortex Development ◽

Excitatory Neurons ◽

Human And Mouse

AbstractBackgroundThe specification and differentiation of neocortical projection neurons is a complex process under precise molecular regulation; however, little is known about the similarities and differences in cerebral cortex development between human and mouse at single-cell resolution.ResultsHere, using single-cell RNA-seq (scRNA-seq) data we explore the divergence and conservation of human and mouse cerebral cortex development using 18,446 and 7,610 neocortical cells. Systematic cross-species comparison reveals that the overall transcriptome profile in human cerebral cortex is similar to that in mouse such as cell types and their markers genes. By single-cell trajectories analysis we find human and mouse excitatory neurons have different developmental trajectories of neocortical projection neurons, ligand-receptor interactions and gene expression patterns. Further analysis reveals a refinement of neuron differentiation that occurred in human but not in mouse, suggesting that excitatory neurons in human undergo refined transcriptional states in later development stage. By contrast, for glial cells and inhibitory neurons we detected conserved developmental trajectories in human and mouse.ConclusionsTaken together, our study integrates scRNA-seq data of cerebral cortex development in human and mouse, and uncovers distinct developing models in neocortical projection neurons. The earlier activation of cognition -related genes in human may explain the differences in behavior, learning or memory abilities between the two species.

Download Full-text

Thyroid hormone regulated genes in cerebral cortex development

Journal of Endocrinology ◽

10.1530/joe-16-0424 ◽

2017 ◽

Vol 232 (2) ◽

pp. R83-R97 ◽

Cited By ~ 45

Author(s):

Juan Bernal

Keyword(s):

Cerebral Cortex ◽

Thyroid Hormones ◽

Fetal Development ◽

Cell Types ◽

Control Of Gene Expression ◽

Cellular Targets ◽

Cerebral Cortex Development ◽

Subplate Neurons ◽

Genes Encoding

The physiological and developmental effects of thyroid hormones are mainly due to the control of gene expression after interaction of T3 with the nuclear receptors. To understand the role of thyroid hormones on cerebral cortex development, knowledge of the genes regulated by T3 during specific stages of development is required. In our laboratory, we previously identified genes regulated by T3 in primary cerebrocortical cells in culture. By comparing these data with transcriptomics of purified cell types from the developing cortex, the cellular targets of T3 can be identified. In addition, many of the genes regulated transcriptionally by T3 have defined roles in cortex development, from which the role of T3 can be derived. This review analyzes the specific roles of T3-regulated genes in the different stages of cortex development within the physiological frame of the developmental changes of thyroid hormones and receptor concentrations in the human cerebral cortex during fetal development. These data indicate an increase in the sensitivity to T3 during the second trimester of fetal development. The main cellular targets of T3 appear to be the Cajal-Retzius and the subplate neurons. On the other hand, T3 regulates transcriptionally genes encoding extracellular matrix proteins, involved in cell migration and the control of diverse signaling pathways.

Download Full-text