The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-06-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/64903 |
| _version_ | 1811252911170125824 |
|---|---|
| author | Emily G Berghoff Lori Glenwinkel Abhishek Bhattacharya HaoSheng Sun Erdem Varol Nicki Mohammadi Amelia Antone Yi Feng Ken Nguyen Steven J Cook Jordan F Wood Neda Masoudi Cyril C Cros Yasmin H Ramadan Denise M Ferkey David H Hall Oliver Hobert |
| author_facet | Emily G Berghoff Lori Glenwinkel Abhishek Bhattacharya HaoSheng Sun Erdem Varol Nicki Mohammadi Amelia Antone Yi Feng Ken Nguyen Steven J Cook Jordan F Wood Neda Masoudi Cyril C Cros Yasmin H Ramadan Denise M Ferkey David H Hall Oliver Hobert |
| author_sort | Emily G Berghoff |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:41:49Z |
| format | Article |
| id | doaj.art-e7ee36d6cc2944a39f18085f7d66c34d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:41:49Z |
| publishDate | 2021-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e7ee36d6cc2944a39f18085f7d66c34d2022-12-22T03:24:45ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.64903The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neuronsEmily G Berghoff0Lori Glenwinkel1Abhishek Bhattacharya2HaoSheng Sun3https://orcid.org/0000-0003-3919-559XErdem Varol4Nicki Mohammadi5Amelia Antone6Yi Feng7Ken Nguyen8Steven J Cook9https://orcid.org/0000-0002-1345-7566Jordan F Wood10Neda Masoudi11Cyril C Cros12Yasmin H Ramadan13Denise M Ferkey14David H Hall15https://orcid.org/0000-0001-8459-9820Oliver Hobert16https://orcid.org/0000-0002-7634-2854Department of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesDepartment of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesDepartment of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesDepartment of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesDepartment of Statistics, Zuckerman Institute, Columbia University, New York, United StatesDepartment of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesDepartment of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesDepartment of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesDepartment of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, United StatesDepartment of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesDepartment of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesDepartment of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesDepartment of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, United StatesDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, United StatesMany 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.https://elifesciences.org/articles/64903neurosciencegeneticstranscription factor |
| spellingShingle | Emily G Berghoff Lori Glenwinkel Abhishek Bhattacharya HaoSheng Sun Erdem Varol Nicki Mohammadi Amelia Antone Yi Feng Ken Nguyen Steven J Cook Jordan F Wood Neda Masoudi Cyril C Cros Yasmin H Ramadan Denise M Ferkey David H Hall Oliver Hobert The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons eLife neuroscience genetics transcription factor |
| title | The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons |
| title_full | The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons |
| title_fullStr | The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons |
| title_full_unstemmed | The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons |
| title_short | The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons |
| title_sort | prop1 like homeobox gene unc 42 specifies the identity of synaptically connected neurons |
| topic | neuroscience genetics transcription factor |
| url | https://elifesciences.org/articles/64903 |
| work_keys_str_mv | AT emilygberghoff theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT loriglenwinkel theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT abhishekbhattacharya theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT haoshengsun theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT erdemvarol theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT nickimohammadi theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT ameliaantone theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT yifeng theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT kennguyen theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT stevenjcook theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT jordanfwood theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT nedamasoudi theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT cyrilccros theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT yasminhramadan theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT denisemferkey theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT davidhhall theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT oliverhobert theprop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT emilygberghoff prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT loriglenwinkel prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT abhishekbhattacharya prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT haoshengsun prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT erdemvarol prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT nickimohammadi prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT ameliaantone prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT yifeng prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT kennguyen prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT stevenjcook prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT jordanfwood prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT nedamasoudi prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT cyrilccros prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT yasminhramadan prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT denisemferkey prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT davidhhall prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons AT oliverhobert prop1likehomeoboxgeneunc42specifiestheidentityofsynapticallyconnectedneurons |