Making sense of neural development by comparing wiring strategies for seeing and hearing

The ability to perceive and interact with the world depends on a diverse array of neural circuits specialized for carrying out specific computations. Each circuit is assembled using a relatively limited number of molecules and common developmental steps, from cell fate specification to activity-dependent synaptic refinement. Given this shared toolkit, how do individual circuits acquire their characteristic properties? We explore this question by comparing development of the circuitry for seeing and hearing, highlighting a few examples where differences in each system’s sensory demands necessitate different developmental strategies.

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Cell fate specification in an in vitro model of neural development

European Journal of Cell Biology ◽

10.1016/s0171-9335(98)80018-6 ◽

1998 ◽

Vol 76 (1) ◽

pp. 63-76 ◽

Cited By ~ 9

Author(s):

Ruth Jostock ◽

Martin Rentrop ◽

Alfred Maelicke

Keyword(s):

Cell Fate ◽

Neural Development ◽

In Vitro Model ◽

Cell Fate Specification ◽

Fate Specification ◽

Vitro Model

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Temporal cell fate determination in the spinal cord is mediated by the duration of Notch signalling

10.1101/2021.10.25.465818 ◽

2021 ◽

Author(s):

Craig T Jacobs ◽

Aarti Kejriwal ◽

Katrinka M Kocha ◽

Kevin Y Jin ◽

Peng Huang

Keyword(s):

Spinal Cord ◽

Cell Fate ◽

Neural Development ◽

Time Windows ◽

Notch Signalling ◽

Cell Fate Specification ◽

Temporal Regulation ◽

Fate Specification ◽

Temporal Differentiation ◽

High Level

During neural development, progenitor cells generate different types of neurons in specific time windows. Despite the characterisation of many of the transcription factor networks involved in these differentiation events, the mechanism behind their temporal regulation is poorly understood. To address this question, we studied the temporal differentiation of the simple lateral floor plate (LFP) domain in the zebrafish spinal cord. LFP progenitors sequentially generate early-born Kolmer-Agduhr″ (KA″) interneurons and late-born V3 interneurons. Analysis using a Notch signalling reporter demonstrates that these cell populations have distinct Notch signalling profiles. Not only do V3 cells receive higher total levels of Notch response, but they collect this response over a longer duration compared to V3 cells. To test whether the duration of Notch signalling determines the temporal cell fate specification, we combined a transgene that constitutively activates Notch signalling in the ventral spinal cord with a heat shock inducible Notch signalling terminator to switch off Notch response at any given time. Sustained Notch signalling results in expanded LFP progenitors while KA″ and V3 interneurons fail to specify. Early termination of Notch signalling leads to exclusively KA″ cell fate, despite the high level of Notch signalling, whereas late attenuation of Notch signalling drives only V3 cell fate. This suggests that the duration of Notch signalling is instructive in cell fate specification. Interestingly, knockdown experiments reveal a role for the Notch ligand Jag2b in maintaining LFP progenitors and limiting their differentiation into KA″ and V3 cells. Our results indicate that Notch signalling is required for neural progenitor maintenance while a specific attenuation timetable defines the fate of the postmitotic progeny.

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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

G3 Genes|Genome|Genetics ◽

10.1534/g3.120.401515 ◽

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.

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