Cornell R et al. (2022) J Neurosci "Conditional degradation of UNC-31/CAPS enables spatiotemporal analysis of neuropeptide function."

Liu J, Cornell R, Pocock R, Cao W

[J Neurosci, 2022]

Neuropeptide release from dense-core vesicles in Caenorhabditis elegans is promoted by UNC-31, ortholog of the calcium-dependent activator protein for secretion (CAPS). Loss of UNC-31 causes multiple phenotypes in C. elegans including reduced motility, retention of late-stage eggs and reduction in evoked synaptic release. However, the ability to analyze UNC-31 function over discrete timescales and in specific neurons is lacking. Here, we generated and validated a tool to enable UNC-31 expression and spatiotemporal functional analysis. We show that endogenously tagged UNC-31 is expressed in major ganglia and nerve cords from late-embryonic stages through to adult. Using the auxin-inducible degradation system, we depleted UNC-31 post-embryonically from the hermaphrodite nervous system and revealed defects in egg-laying, locomotion and vesicle release that were comparable to unc-31 null mutant animals. In addition, we found that depleting UNC-31 specifically from the BAG sensory neurons causes increased intestinal fat storage, highlighting the spatial sensitivity of this system. Together, this protein degradation tool may be used to facilitate studies of neuropeptide function at precise cellular and temporal scales.SIGNIFICANCE STATEMENT:Animal behavior and physiology is controlled by neuropeptides that are released from specific neuronal sources. The ability to dissect discrete neuropeptide functions requires precise manipulation of neuropeptide release. We have developed and validated a tool that enables precise spatiotemporal regulation of neuropeptide release that will enable researchers to examine neuropeptide function at exceptional resolution.

Cornell R et al. (2024) Nat Commun "Neuro-intestinal acetylcholine signalling regulates the mitochondrial stress response in Caenorhabditis elegans."

Godini R, Harradine B, Cao W, Pocock R, Handley A, Cornell R

[Nat Commun, 2024]

Neurons coordinate inter-tissue protein homeostasis to systemically manage cytotoxic stress. In response to neuronal mitochondrial stress, specific neuronal signals coordinate the systemic mitochondrial unfolded protein response (UPR^mt) to promote organismal survival. Yet, whether chemical neurotransmitters are sufficient to control the UPR^mt in physiological conditions is not well understood. Here, we show that gamma-aminobutyric acid (GABA) inhibits, and acetylcholine (ACh) promotes the UPR^mt in the Caenorhabditis elegans intestine. GABA controls the UPR^mt by regulating extra-synaptic ACh release through metabotropic GABA_B receptors GBB-1/2. We find that elevated ACh levels in animals that are GABA-deficient or lack ACh-degradative enzymes induce the UPR^mt through ACR-11, an intestinal nicotinic α7 receptor. This neuro-intestinal circuit is critical for non-autonomously regulating organismal survival of oxidative stress. These findings establish chemical neurotransmission as a crucial regulatory layer for nervous system control of systemic protein homeostasis and stress responses.

Etemad-Moghadam B et al. (1994) Worm Breeder's Gazette "PAR-3 is a Novel Maternally Encoded Protein"

Etemad-Moghadam B, Kemphues KJ

[Worm Breeder's Gazette, 1994]

PAR-3 IS A NOVEL MATERNALLY ENCODED PROTEIN. Bijan Etemad-Moghadam and Kenneth Kemphues, Cornell University, Ithaca New York.

Guo S et al. (1994) Worm Breeder's Gazette "Identification of par-1 Gene by Injecting in vitro-transcribed anti-sense RNA"

Guo S, Kemphues KJ

[Worm Breeder's Gazette, 1994]

Identification of par-l gene by injecting in vitro- transcribed anti-sense RNA Su Guo, Kenneth Kemphues, Dept. of Genetics & Development, Cornell University, Ithaca, NY 14853

Caron C et al. (1994) Worm Breeder's Gazette "Analysis of zyg-1, a Gene Required During the First Embryonic Divisions and For Formation of a Functional Vulva"

Caron C, Kemphues KJ

[Worm Breeder's Gazette, 1994]

ANALYSIS OF zyg-1, A GENE REQUIRED DURING THE FIRST EMBRYONIC DIVISIONS AND FOR FORMATION OF A FUNCTIONAL VULVA. Cathy Caron and Kenneth Kemphues, Cornell University, Ithaca, New York.

Watts JL et al. (1994) Worm Breeder's Gazette "zu170 Defines a New Gene, par-6, and Can Act as a Suppressor of par-2"

Watts JL, Kemphues KJ

[Worm Breeder's Gazette, 1994]

zul70 defines a new gene, par-6, and can act as a suppressor of par-2 Jennifer Watts and Ken Kemphues Genetics and Development, Cornell University, Ithaca NY 14853

Boyd L et al. (1994) Worm Breeder's Gazette "Asymmetric PAR-2 at First Cleavage"

Boyd L, Kemphues KJ, Levitan DJ

[Worm Breeder's Gazette, 1994]

Asymmetric PAR-2 at First Cleavage Lynn Boyd1, Diane Levitan2, and Ken Kemphues1, 1)Section of Genetics and Development, Cornell University; 2) Department of Cellular and Developmental Biology, Harvard University (current address: Columbia University)

Thirumaran P et al. (2024) MicroPubl Biol "Endogenous fluorescent reporters for heat shock proteins are not detectable after stress induction."

Cornell R, Thirumaran P, Pocock R

[MicroPubl Biol, 2024]

Mitochondria and the endoplasmic reticulum (ER) utilise unique unfolded protein response (UPR) mechanisms to maintain cellular proteostasis. Heat shock proteins (HSPs) are UPR chaperones induced by specific stressors to promote protein folding. Previous research has successfully employed transgenic reporters in <i>Caenorhabditis elegans</i> to report HSP induction. However, transgenic reporters are overexpressed and only show promoter regulation and not post-transcriptional regulation. To examine endogenous HSP regulation, we attempted to generate and validate endogenous reporters for mitochondrial ( HSP-60 ) and ER ( HSP-4 ) chaperones. Using CRISPR/Cas9 technology, F2A-GFP-H2B coding DNA was inserted downstream of each HSP gene and stress induction assays conducted to validate these tools. Endogenous reporters were successfully generated for <i>hsp-4</i> and <i>hsp-60</i> . However, GFP induction could not be detected with these endogenous reporters upon stress induction, likely due to low level expression.

Moreira, P. et al. (2019) International Worm Meeting "Decoding the role of the NFY transcription factor in brain development."

Cornell, R., Deng, J., Moreira, P., Pocock, R.

[International Worm Meeting, 2019]

The establishment of correct brain architecture during development is an exceptionally complex process requiring precisely controlled cell specification, migration, axon outgrowth and guidance. These events are controlled by multiple transcription factors, conserved guidance systems and environmental cues. The Caenorhabditis elegans nervous system is an excellent model to study brain development due to its relative simplicity and conserved nature of development. My PhD project aims to identify molecular mechanisms that drive brain development. Using an unbiased genetic screen, we identified a Nuclear Factor Y transcriptional complex (NFY) that controls the development of a pair of glutamatergic interneurons. The NFY family is one of the most abundant and conserved transcription factors in eukaryotes and is involved in the regulation genes associated with several developmental steps. The NFY trimeric complex comprises the conserved NFY-A, -B and -C subunits that regulate gene expression through binding specific motifs in promoter regions. Our preliminary data show that the NFY complex regulates neuronal fate and axon guidance of specific neurons. Using single-cell resolution analysis, transcriptomics and ChIP sequencing I will decipher the molecular mechanism(s) through which NFYs control neuronal development.

Galindo-Malagn XA et al. (2022) Zootaxa "New species, synonymies and records in the genus Rhagovelia Mayr, 1865 (Hemiptera: Heteroptera: Veliidae) from Colombia."

Moreira FFF, Morales I, Mondragn-F SP, Galindo-Malagn XA

[Zootaxa, 2022]

Rhagovelia medinae sp. nov., of the hambletoni group (angustipes complex), and R. utria sp. nov., of the hirtipes group (robusta complex), are described, illustrated, and compared with similar congeners. Based on the examination of type specimens, six new synonymies are proposed: R. elegans Uhler, 1894 = R. pediformis Padilla-Gil, 2010, syn. nov.; R. cauca Polhemus, 1997 = R. azulita Padilla-Gil, 2009, syn. nov., R. huila Padilla-Gil, 2009, syn. nov., R. oporapa Padilla-Gil, 2009, syn. nov, R. quilichaensis Padilla-Gil, 2011, syn. nov.; and R. gaigei, Drake Hussey, 1947 = R. victoria Padilla-Gil, 2012 syn. nov. The first record from Colombia is presented for R. trailii (White, 1879), and the distributions of the following species are extended in the country: R. cali Polhemus, 1997, R. castanea Gould, 1931, R. cauca Polhemus, 1997, R. gaigei Drake Hussey, 1957, R. elegans Uhler, 1894, R. femoralis Champion, 1898, R. malkini Polhemus, 1997, R. perija Polhemus, 1997, R. sinuata Gould, 1931, R. venezuelana Polhemus, 1997, R. williamsi Gould, 1931, and R. zeteki Drake, 1953.