Integration of Spatial and Temporal Patterning in the Invertebrate and Vertebrate Nervous System

Abstract

The nervous system is one of the most sophisticated animal tissues, consisting of thousands of interconnected cell types. How the nervous system develops its diversity from a few neural stem cells remains a challenging question. Spatial and temporal patterning mechanisms provide an efficient model through which diversity can be generated. The molecular mechanism of spatiotemporal patterning has been studied extensively in Drosophila melanogaster, where distinct sets of transcription factors define the spatial domains and temporal windows that give rise to different cell types. Similarly, in vertebrates, spatial domains defined by transcription factors produce different types of neurons in the brain and neural tube. At the same time, different cortical neuronal types are generated within the same cell lineage with a specific birth order. However, we still do not understand how the orthogonal information of spatial and temporal patterning is integrated into the progenitor and post-mitotic cells to combinatorially give rise to different neurons. In this review, after introducing spatial and temporal patterning in Drosophila and mice, we discuss possible mechanisms that neural progenitors may use to integrate spatial and temporal information. We finally review the functional implications of spatial and temporal patterning and conclude envisaging how small alterations of these mechanisms can lead to the evolution of new neuronal cell types.

Neuron types in the developing mouse brain are divided into partially matching epigenomic and transcriptomic classes

“…Consistent with the NT-type results, the markers for the cell types present in the diencephalon, mid- and hindbrain at E14.5 were differentially expressed in clusters (Figure 4). The final number of scATAC-seq cell clusters (n=189) matches well with the expectation to find the 6 neuron classes as well as the neuronal progenitors, while each neuron type can be present in several stages of neurogenesis and maturation in E14.5 mouse brain, which is further divided into dorso-ventral (7 domains) and anterior-posterior (4-5 domains) molecularly distinct domains and may give rise to temporal sublineages 25–27 . Importantly, the categorization by neurotransmitter identity reveals broad classes of neurons, while distinguishing the whole range of molecular identities would require an improved set of markers.…”

“…Here, the topology of the cell type tree can provide a measure of developmental and evolutionary relatedness of cell types 3–5 : Specific patterns of genomic feature expression - or enhancer use - along the branches of a cell type tree can reveal genetic regulatory logic. For example, it has been shown that neurotransmitter phenotype can be associated with multiple TF combinations in Drosophila and C. elegans , and that the expression pattern of neural differentiation genes are better explained by a model where each gene can be regulated by several TFs 6,7 . The examples of such phenotypic convergence are still rare in vertebrates, however the divergence between lineage relatedness and final acquired cellular phenotype has been demonstrated in zebrafish lineage tracing studies 8,9 .…”

A chromatin remodelling SWI/SNF subunit, Snr1, regulates neural stem cell determination and differentiation

“…Some patterning genes are expressed at distinct time points from the generation of neurons while still influencing the type of daughter cell generated, indicating transcriptional memory ( Erclik et al, 2017 ; Konstantinides et al, 2022 ). It has been proposed that unique chromatin states exist in neuroblasts expressing the same transcription factors ( Chen and Konstantinides, 2022 ; El-Danaf et al, 2023 ; Janssens et al, 2022 ; Rossi et al, 2021 ; Sen, 2023 ). Although there is support for a model of chromatin state heterogeneity, how these are generated and maintained remains an open question.…”

Evolution of patterning

“…Temporal transcription factor series have been described in different contexts [48], but nowhere nearly as comprehensively as in the Drosophila developing optic lobe [49,50]. As mentioned earlier, the transcription factors that are expressed temporally in the Drosophila ventral nerve cord neuronal stem cells are also expressed along the AP axis of the blastoderm embryo like gap genes (Fig.…”