cnd-1/NeuroD1 Functions with the Homeobox Geneceh-5/Vax2 and Hox Geneceh-13/labial To Specify Aspects of RME and DD Neuron Fate inCaenorhabditis elegans

Abstract

Identifying the mechanisms behind neuronal fate specification are key to understanding normal neural development in addition to neurodevelopmental disorders such as autism and schizophrenia. In vivo cell fate specification is difficult to study in vertebrates. However, the nematode Caenorhabditis elegans, with its invariant cell lineage and simple nervous system of 302 neurons, is an ideal organism to explore the earliest stages of neural development. We used a comparative transcriptome approach to examine the role of cnd-1/NeuroD1 in C. elegans nervous system development and function. This basic helix-loop-helix transcription factor is deeply conserved across phyla and plays a crucial role in cell fate specification in both the vertebrate nervous system and pancreas. We find that cnd-1 controls expression of ceh-5, a Vax2-like homeobox class transcription factor, in the RME head motorneurons and PVQ tail interneurons. We also show that cnd-1 functions redundantly with the Hox gene ceh-13/labial in defining the fate of DD1 and DD2 embryonic ventral nerve cord motorneurons. These data highlight the utility of comparative transcriptomes for identifying transcription factor targets and understanding gene regulatory networks.

A lineage-resolved cartography of microRNA promoter activity in C. elegans empowers multidimensional developmental analysis

“…13C ). For example, miR-43-44, a neuron-specific miRNA, was bound by CND-1/NEUROD1, a motor neuron fate determinant 89 , 90 , while miR-2, a muscle-specific miRNA, was bound by HLH-1/MYF6 and HND-1/PTF1A, two critical TFs that specify body wall muscle fate 91 (Fig. 7B , Supplementary Fig.…”

“…To validate whether tissue fate determinants are required for miRNA expression, we focused on known determinants of five major tissue types: CND-1 (a subset of neurons) 89 , 90 ; PHA-4 (pharynx) 74 , 92 ; ELT-1 (skin) 93 ; HLH-1, HND-1, and UNC-120 (muscle) 91 ; and ELT-2 (intestine) 94 . We perturbed these TFs using loss-of-function alleles or RNAi and quantified in nine experiment sets the cellular expression of tissue-specific miRNAs.…”

Emerging Roles for Hox Proteins in the Last Steps of Neuronal Development in Worms, Flies, and Mice

“…The role of the anterior Hox gene ceh-13 during C. elegans neuronal terminal differentiation is largely elusive, partly due to the early larval lethality of ceh-13 mutants (Brunschwig et al, 1999). A recent study suggested ceh-13 controls terminal identity features of GABAergic motor neurons (DD1, DD2) located in the anterior ganglion, but the underlying mechanisms remain unknown (Aquino-Nunez et al, 2020).…”

microRNA‐124 regulates Notch and NeuroD1 to mediate transition states of neuronal development

“…Out of all the conserved proteins, none of the family member of NeuroD have been incorporated into the sea urchin neuronal GRN. NeuroD (NeuroD1, NeuroD2, and NeuroD6) TFs are members of the neuronal lineage basic helix‐loop‐helix family that regulate the transition from neuronal differentiation to maturation in vertebrate/invertebrate systems (Amador‐Arjona et al., 2015; Aquino‐Nunez et al., 2020; Cho & Tsai, 2004; Huang et al., 2011; Liu et al., 2011; Masoudi et al., 2018; Matsuda et al., 2019; Pataskar et al., 2016). NeuroD1, specifically, is expressed early in mammalian embryos to regulate neuronal development, suggesting that it is a good candidate to be incorporated into the sea urchin neuronal GRN (Matsuda et al., 2019; Pataskar et al., 2016; Tutukova, Tarabykin, & Hernandez‐Miranda, 2021).…”