Biology subjects

Cao, W. X.

Publications and source records attributed to Cao, W. X..

5 recordsLinked to original sources

bioRxiv2025

PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons of C. elegans

FoxA transcription factors pattern gut tissue across animal phylogeny. Beyond their early patterning function, little is known about whether they control the terminal differentiation and/or function of the fully mature enteric nervous system, the intrinsic nervous system of the gut. We show here that the expression and function of the sole C. elegans FoxA homolog, PHA-4, reaches beyond its previously described pioneer factor roles in patterning the foregut. Through the engineering of neuron-specific cis-regulatory alleles, Cre-mediated cell-specific knockouts and degron-mediated, temporally controlled PHA-4/FoxA removal in postmitotic neurons, we found that PHA-4/FoxA is required not only to initiate the terminal differentiation program of foregut-associated enteric neurons, but also to maintain their functional properties throughout the life of the animal. Moreover, we discovered novel sites of expression of PHA-4/FoxA in extrapharyngeal enteric neurons that innervate the hindgut (AVL and DVB), a GABAergic interneuron that controls foregut function during sleep (RIS), and a peptidergic neuron, PVT, which we implicate here in controlling defecation behavior. We show that while PHA-4/FoxA is not required for the developmental specification of AVL, DVB, RIS, and PVT, it is required to enable these neurons to control enteric functions. Taken together, pha-4 is the only transcription factor known to date that is expressed in and required for the proper function of all distinct types of enteric neurons in a nervous system.

neuroscience↗

bioRxiv2024

Comparative analysis of new, mScarlet-based red fluorescent tags in Caenorhabditis elegans

One problem that has hampered the use of red fluorescent proteins in the fast-developing nematode C. elegans has been the substantial time delay in maturation of several generations of red fluorophores. The recently described mScarlet-I3 protein has properties that may overcome this limitation. We compare here the brightness and maturation time of CRISPR/Cas9 genome-engineered mScarlet, mScarlet3, mScarlet-I3 and GFP reporter knock-ins. Comparing the onset and brightness of expression of reporter alleles of C. elegans golg-4, encoding a broadly expressed Golgi resident protein, we found that the onset of detection of mScarlet-I3 in the embryo is several hours earlier than older versions of mScarlet and comparable to GFP. These findings were further supported by comparing mScarlet-I3 and GFP reporter alleles for pks-1, a gene expressed in the CAN neuron and cells of the alimentary system, as well as reporter alleles for the panneuronal, nuclear marker unc-75. Hence, the relative properties of mScarlet-I3 and GFP do not depend on cellular or subcellular context. In all cases, mScarlet-I3 reporters also show improved signal-to-noise ratio compared to GFP.

genetics↗

bioRxiv2021

The enteric nervous system of C. elegans is specified by the Sine Oculis-like homeobox gene ceh-34

Overarching themes in the terminal differentiation of the enteric nervous system, an autonomously acting unit of animal nervous systems, have so far eluded discovery. We describe here the overall regulatory logic of enteric nervous system differentiation of the nematode C. elegans that resides within the foregut (pharynx) of the worm. A Caenorhabditis elegans homolog of the Drosophila Sine Oculis homeobox gene, ceh-34, is expressed in all 14 classes of interconnected pharyngeal neurons from their birth throughout their life time, but in no other neuron type of the entire animal. Constitutive and temporally controlled ceh-34 removal shows that ceh-34 is required to initiate and maintain the neuron type-specific terminal differentiation program of all pharyngeal neuron classes, including their circuit assembly, without affecting panneuronal features. Through additional genetic loss of function analysis, we show that within each pharyngeal neuron class, ceh-34 cooperates with different homeodomain transcription factors to individuate distinct pharyngeal neuron classes. Our analysis underscores the critical role of homeobox genes in neuronal identity specification and links them to the control of neuronal circuit assembly of the enteric nervous system. Together with the pharyngeal nervous system simplicity as well as its specification by a Sine Oculis homolog, our findings invite speculations about the early evolution of nervous systems.

neuroscience↗

bioRxiv2020

The RNA-binding protein, Rasputin/G3BP, enhances the stability and translation of its target mRNAs

G3BP RNA-binding proteins are important components of stress granules (SGs). Here we analyze the role of Drosophila G3BP, Rasputin (RIN), in unstressed cells, where RIN is not SG associated. Immunoprecipitation followed by microarray analysis identified over 550 mRNAs that copurify with RIN. The mRNAs found in SGs are long and translationally silent. In contrast, we find that RIN-bound mRNAs, which encode core components of the transcription, splicing and translation machinery, are short, stable and highly translated. We show that RIN is associated with polysomes and provide evidence for a direct role for RIN and its human homologs in stabilizing and upregulating the translation of their target mRNAs. We propose that when cells are stressed the resulting incorporation of RIN/G3BPs into SGs sequesters them away from their short target mRNAs. This would downregulate the expression of these transcripts, even though they are not incorporated into stress granules.

genomics↗

bioRxiv2019

Precise temporal regulation of post-transcriptional repressors is required for an orderly Drosophila maternal-to-zygotic transition

In animal embryos the maternal-to-zygotic transition (MZT) hands developmental control from maternal to zygotic gene products. We show that the maternal proteome represents over half of the protein coding capacity of the Drosophila melanogaster genome and that 2% of this proteome is rapidly degraded during the MZT. Cleared proteins include the post-transcriptional repressors Cup, Trailer hitch (TRAL), Maternal expression at 31B (ME31B), and Smaug (SMG). While the ubiquitin-proteasome system is necessary for clearance of all four repressors, distinct E3 ligase complexes target them: the C-terminal to Lis1 Homology (CTLH) complex targets Cup, TRAL and ME31B for degradation early in the MZT; the Skp/Cullin/F-box-containing (SCF) complex targets SMG at the end of the MZT. Deleting the C-terminal 233 amino acids of SMG makes the protein immune to degradation. We show that artificially persistent SMG downregulates the zygotic re-expression of mRNAs whose maternal contribution is cleared by SMG. Thus, clearance of SMG permits an orderly MZT.

developmental biology↗