The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons

eLife

Steven J Cook¹  Yi Feng¹  Yasmin H Ramadan¹  Oliver Hobert¹  Emily G Berghoff¹  Lori Glenwinkel¹  Cyril C Cros¹  Amelia Antone¹  Abhishek Bhattacharya¹  Nicki Mohammadi¹  HaoSheng Sun¹  Neda Masoudi¹  Jordan F Wood²  Denise M Ferkey²  Erdem Varol³  Ken Nguyen⁴  David H Hall⁴ 

[1] Department of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United States;Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, United States;Department of Statistics, Zuckerman Institute, Columbia University, New York, United States;Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United States;

关键词: neuroscience;    genetics;    transcription factor;    C. elegans;   

DOI  :  10.7554/eLife.64903

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Many neuronal identity regulators are expressed in distinct populations of cells in the nervous system, but their function is often analyzed only in specific isolated cellular contexts, thereby potentially leaving overarching themes in gene function undiscovered. We show here that the Caenorhabditis elegans Prop1-like homeobox gene unc-42 is expressed in 15 distinct sensory, inter- and motor neuron classes throughout the entire C. elegans nervous system. Strikingly, all 15 neuron classes expressing unc-42 are synaptically interconnected, prompting us to investigate whether unc-42 controls the functional properties of this circuit and perhaps also the assembly of these neurons into functional circuitry. We found that unc-42 defines the routes of communication between these interconnected neurons by controlling the expression of neurotransmitter pathway genes, neurotransmitter receptors, neuropeptides, and neuropeptide receptors. Anatomical analysis of unc-42 mutant animals reveals defects in axon pathfinding and synaptic connectivity, paralleled by expression defects of molecules involved in axon pathfinding, cell-cell recognition, and synaptic connectivity. We conclude that unc-42 establishes functional circuitry by acting as a terminal selector of functionally connected neuron types. We identify a number of additional transcription factors that are also expressed in synaptically connected neurons and propose that terminal selectors may also function as ‘circuit organizer transcription factors’ to control the assembly of functional circuitry throughout the nervous system. We hypothesize that such organizational properties of transcription factors may be reflective of not only ontogenetic, but perhaps also phylogenetic trajectories of neuronal circuit establishment.

【 授权许可】

CC BY