scholarly journals ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System

2020 ◽  
Vol 10 (6) ◽  
pp. 1949-1962 ◽  
Author(s):  
Elyse L. Christensen ◽  
Alexandra Beasley ◽  
Jessica Radchuk ◽  
Zachery E. Mielko ◽  
Elicia Preston ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factors ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Neural Development ◽  
System Development ◽  
Neuronal Cell ◽  
Nervous System Development ◽  
Link Type ◽  
Neuroblast Migration

Proper nervous system development is required for an organism’s survival and function. Defects in neurogenesis have been linked to neurodevelopmental disorders such as schizophrenia and autism. Understanding the gene regulatory networks that orchestrate neural development, specifically cascades of proneural transcription factors, can better elucidate which genes are most important during early neurogenesis. Neurogenins are a family of deeply conserved factors shown to be both necessary and sufficient for the development of neural subtypes. However, the immediate downstream targets of neurogenin are not well characterized. The objective of this study was to further elucidate the role of ngn-1/neurogenin in nervous system development and to identify its downstream transcriptional targets, using the nematode Caenorhabditis elegans as a model for this work. We found that ngn-1 is required for axon outgrowth, nerve ring architecture, and neuronal cell fate specification. We also showed that ngn-1 may have roles in neuroblast migration and epithelial integrity during embryonic development. Using RNA sequencing and comparative transcriptome analysis, we identified eight transcription factors (hlh-34/NPAS1, unc-42/PROP1, ceh-17/PHOX2A, lim-4/LHX6, fax-1/NR2E3, lin-11/LHX1, tlp-1/ZNF503, and nhr-23/RORB) whose transcription is activated, either directly or indirectly, by ngn-1. Our results show that ngn-1 has a role in transcribing known terminal regulators that establish and maintain cell fate of differentiated neural subtypes and confirms that ngn-1 functions as a proneural transcription factor in C. elegans neurogenesis.

scholarly journals cnd-1/NeuroD1 Functions with the Homeobox Gene ceh-5/Vax2 and Hox Gene ceh-13/labial To Specify Aspects of RME and DD Neuron Fate in Caenorhabditis elegans

2020 ◽  
Vol 10 (9) ◽  
pp. 3071-3085
Author(s):  
Wendy Aquino-Nunez ◽  
Zachery E Mielko ◽  
Trae Dunn ◽  
Elise M Santorella ◽  
Ciara Hosea ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Neural Development ◽  
Nervous System Development ◽  
Cell Fate Specification ◽  
Hox Gene ◽  
Fate Specification

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.

scholarly journals Development in the Mammalian Auditory System Depends on Transcription Factors

2021 ◽  
Vol 22 (8) ◽  
pp. 4189
Author(s):  
Karen L. Elliott ◽  
Gabriela Pavlínková ◽  
Victor V. Chizhikov ◽  
Ebenezer N. Yamoah ◽  
Bernd Fritzsch
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Auditory System ◽  
Hair Cells ◽  
System Development ◽  
Neuronal Cell ◽  
Spiral Ganglion Neuron ◽  
Cochlear Hair Cells ◽  
Cochlear Nuclei ◽  
Bhlh Genes

We review the molecular basis of several transcription factors (Eya1, Sox2), including the three related genes coding basic helix–loop–helix (bHLH; see abbreviations) proteins (Neurog1, Neurod1, Atoh1) during the development of spiral ganglia, cochlear nuclei, and cochlear hair cells. Neuronal development requires Neurog1, followed by its downstream target Neurod1, to cross-regulate Atoh1 expression. In contrast, hair cells and cochlear nuclei critically depend on Atoh1 and require Neurod1 expression for interactions with Atoh1. Upregulation of Atoh1 following Neurod1 loss changes some vestibular neurons’ fate into “hair cells”, highlighting the significant interplay between the bHLH genes. Further work showed that replacing Atoh1 by Neurog1 rescues some hair cells from complete absence observed in Atoh1 null mutants, suggesting that bHLH genes can partially replace one another. The inhibition of Atoh1 by Neurod1 is essential for proper neuronal cell fate, and in the absence of Neurod1, Atoh1 is upregulated, resulting in the formation of “intraganglionic” HCs. Additional genes, such as Eya1/Six1, Sox2, Pax2, Gata3, Fgfr2b, Foxg1, and Lmx1a/b, play a role in the auditory system. Finally, both Lmx1a and Lmx1b genes are essential for the cochlear organ of Corti, spiral ganglion neuron, and cochlear nuclei formation. We integrate the mammalian auditory system development to provide comprehensive insights beyond the limited perception driven by singular investigations of cochlear neurons, cochlear hair cells, and cochlear nuclei. A detailed analysis of gene expression is needed to understand better how upstream regulators facilitate gene interactions and mammalian auditory system development.

scholarly journals Complex Cooperative Functions of Heparan Sulfate Proteoglycans Shape Nervous System Development in Caenorhabditis elegans

2014 ◽  
Vol 4 (10) ◽  
pp. 1859-1870 ◽  
Author(s):  
Carlos A. Díaz-Balzac ◽  
María I. Lázaro-Peña ◽  
Eillen Tecle ◽  
Nathali Gomez ◽  
Hannes E. Bülow
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Heparan Sulfate ◽  
System Development ◽  
Nervous System Development ◽  
Heparan Sulfate Proteoglycans

Spalt modifies EGFR-mediated induction of chordotonal precursors in the embryonic PNS of Drosophila promoting the development of oenocytes

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 711-722 ◽  
Author(s):  
T.E. Rusten ◽  
R. Cantera ◽  
J. Urban ◽  
G. Technau ◽  
F.C. Kafatos ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Fate ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Dual Function ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
And Migration

Genes of the spalt family encode nuclear zinc finger proteins. In Drosophila melanogaster, they are necessary for the establishment of head/trunk identity, correct tracheal migration and patterning of the wing imaginal disc. Spalt proteins display a predominant pattern of expression in the nervous system, not only in Drosophila but also in species of fish, mouse, frog and human, suggesting an evolutionarily conserved role for these proteins in nervous system development. Here we show that Spalt works as a cell fate switch between two EGFR-induced cell types, the oenocytes and the precursors of the pentascolopodial organ in the embryonic peripheral nervous system. We show that removal of spalt increases the number of scolopodia, as a result of extra secondary recruitment of precursor cells at the expense of the oenocytes. In addition, the absence of spalt causes defects in the normal migration of the pentascolopodial organ. The dual function of spalt in the development of this organ, recruitment of precursors and migration, is reminiscent of its role in tracheal formation and of the role of a spalt homologue, sem-4, in the Caenorhabditis elegans nervous system.

scholarly journals aPKC in neuronal differentiation, maturation and function

2019 ◽  
Vol 3 (3) ◽  
Author(s):  
Sophie M. Hapak ◽  
Carla V. Rothlin ◽  
Sourav Ghosh
Keyword(s):  
Nervous System ◽  
Protein Kinase ◽  
Neural Development ◽  
System Development ◽  
Nervous System Development ◽  
Versus Gene ◽  
Metabolic Functions ◽  
Neuropsychiatric Diseases ◽  
And Function ◽  
Neuronal Functions

Abstract The atypical Protein Kinase Cs (aPKCs)—PRKCI, PRKCZ and PKMζ—form a subfamily within the Protein Kinase C (PKC) family. These kinases are expressed in the nervous system, including during its development and in adulthood. One of the aPKCs, PKMζ, appears to be restricted to the nervous system. aPKCs are known to play a role in a variety of cellular responses such as proliferation, differentiation, polarity, migration, survival and key metabolic functions such as glucose uptake, that are critical for nervous system development and function. Therefore, these kinases have garnered a lot of interest in terms of their functional role in the nervous system. Here we review the expression and function of aPKCs in neural development and in neuronal maturation and function. Despite seemingly paradoxical findings with genetic deletion versus gene silencing approaches, we posit that aPKCs are likely candidates for regulating many important neurodevelopmental and neuronal functions, and may be associated with a number of human neuropsychiatric diseases.

scholarly journals Cbln1 regulates axon growth and guidance in multiple neural regions

2021 ◽  
Author(s):  
Sheng-Jian Ji ◽  
Peng Han ◽  
Yuanchu She ◽  
Zhuoxuan Yang ◽  
Mengru Zhuang ◽  
...  
Keyword(s):  
Nervous System ◽  
Axon Guidance ◽  
Neural Development ◽  
System Development ◽  
Axon Growth ◽  
Nervous System Development ◽  
Precise Control ◽  
Commissural Neurons ◽  
Guidance Cues ◽  
Guidance Cue

The accurate construction of neural circuits requires the precise control of axon growth and guidance, which is regulated by multiple growth and guidance cues during early nervous system development. It is generally thought that the growth and guidance cues that control the major steps of axon guidance have been defined. Here, we describe cerebellin-1 (Cbln1) as a novel cue that controls diverse aspects of axon growth and guidance throughout the central nervous system (CNS). Cbln1 has previously been shown to function in late neural development to influence synapse organization. Here we find that Cbln1 has an essential role in early neural development. Cbln1 is expressed on the axons and growth cones of developing commissural neurons and functions in an autocrine manner to promote axon growth. Cbln1 is also expressed in intermediate target tissues and functions as an attractive guidance cue. We find that these functions of Cbln1 are mediated by neurexin-2 (Nrxn2), which functions as the Cbln1 receptor for axon growth and guidance. In addition to the developing spinal cord, we further show that Cbln1 functions in diverse parts of the CNS with major roles in cerebellar parallel fiber growth and retinal ganglion cell axon guidance. Despite the prevailing role of Cbln1 as a synaptic organizer, our study discovers a new and unexpected function for Cbln1 as a general axon growth and guidance cue throughout the nervous system.

scholarly journals Regulation of Gliogenesis by lin-32/Atoh1 in Caenorhabditis elegans

2020 ◽  
Vol 10 (9) ◽  
pp. 3271-3278 ◽  
Author(s):  
Albert Zhang ◽  
Kentaro Noma ◽  
Dong Yan
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Embryonic Development ◽  
Molecular Mechanisms ◽  
System Development ◽  
Nervous System Development ◽  
Proneural Gene ◽  
C Elegans ◽  
Fundamental Process ◽  
Mutant Phenotypes

Abstract The regulation of gliogenesis is a fundamental process for nervous system development, as the appropriate glial number and identity is required for a functional nervous system. To investigate the molecular mechanisms involved in gliogenesis, we used C. elegans as a model and identified the function of the proneural gene lin-32/Atoh1 in gliogenesis. We found that lin-32 functions during embryonic development to negatively regulate the number of AMsh glia. The ectopic AMsh cells at least partially arise from cells originally fated to become CEPsh glia, suggesting that lin-32 is involved in the specification of specific glial subtypes. Moreover, we show that lin-32 acts in parallel with cnd-1/ NeuroD1 and ngn-1/ Neurog1 in negatively regulating an AMsh glia fate. Furthermore, expression of murine Atoh1 fully rescues lin-32 mutant phenotypes, suggesting lin-32/Atoh1 may have a conserved role in glial specification.

scholarly journals Neuronal cell fate diversification controlled by sub-temporal action of Kruppel

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Johannes Stratmann ◽  
Hugo Gabilondo ◽  
Jonathan Benito-Sipos ◽  
Stefan Thor
Keyword(s):  
Cell Fate ◽  
System Development ◽  
Neuronal Cell ◽  
Cell Types ◽  
Nervous System Development ◽  
Spatial Cues ◽  
Distinct Cell ◽  
Embryonic Nervous System ◽  
The Many ◽  
Temporal Program

During Drosophila embryonic nervous system development, neuroblasts express a programmed cascade of five temporal transcription factors that govern the identity of cells generated at different time-points. However, these five temporal genes fall short of accounting for the many distinct cell types generated in large lineages. Here, we find that the late temporal gene castor sub-divides its large window in neuroblast 5–6 by simultaneously activating two cell fate determination cascades and a sub-temporal regulatory program. The sub-temporal program acts both upon itself and upon the determination cascades to diversify the castor window. Surprisingly, the early temporal gene Kruppel acts as one of the sub-temporal genes within the late castor window. Intriguingly, while the temporal gene castor activates the two determination cascades and the sub-temporal program, spatial cues controlling cell fate in the latter part of the 5–6 lineage exclusively act upon the determination cascades.

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