Wiring an animal brain is a complex process involving a staggering number of cell-types born at different times and locations in the developing brain. Incorporation of these cells into precise circuits with high fidelity is critical for animal survival and behavior. Assembly of neuronal circuits is heavily dependent upon proper timing of wiring programs, requiring neurons to express specific sets of genes (sometimes transiently) at the right time in development. While cell-type specificity of genetic programs regulating wiring has been studied in detail, mechanisms regulating proper timing and coordination of these programs across cell-types are only just beginning to emerge. In this review, we discuss some temporal regulators of wiring programs and how their activity is controlled over time and space. A common feature emerges from these temporal regulators - they are induced by cell-extrinsic cues and control transcription factors capable of regulating a highly cell-type specific set of target genes. Target specificity in these contexts comes from cell-type specific transcription factors. We propose that the spatiotemporal specificity of wiring programs is controlled by the combinatorial activity of temporal programs and cell-type specific transcription factors. Going forward, a better understanding of temporal regulators will be key to understanding the mechanisms underlying brain wiring, and will be critical for the development of in vitro models like brain organoids.
AbbreviationsC. elegansCaenorhabditis elegans
scRNA-Seqsingle-cell Ribonucleic Acid sequencing
Sygsynaptogenesis abnormal
N-CadherinNeural Cadherin
S1Primary somatosensory cortex
SynGAPSynaptic Ras GTPase activating protein
Ftz-f1Fushi tarazu transcription factor 1
EREEstrogen response element
Npas4Neuronal PAS domain protein 4
BDNFBrain-derived neurotrophic factor
Frmpd3FERM And PDZ Domain Containing 3
Igsf9bImmunoglobulin Superfamily Member 9B
OSNOlfactory sensory neuron
TGF-βTransforming growth factor beta
NF- κBNuclear factor kappa B
NCAMNeural cell adhesion molecule
dprdefective proboscis response
ATAC-SeqAssay for transposase accessible chromatin with high-throughput sequencing
KeywordsNeurodevelopment
Brain wiring
Transcriptional control
Temporal specificity
Hormones
Neuronal activity
© 2022 The Author(s). Published by Elsevier Ltd.
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