Notch signaling plays a well-described role in regulating the formation of neurons from proliferative neural precursors in vertebrates but whether, as in flies, it also specifies sibling cells for different neuronal fates is not known. Ventral spinal cord precursors called pMN cells produce mostly motoneurons and oligodendrocytes, but recent lineage-marking experiments reveal that they also make astrocytes, ependymal cells and interneurons. Our own clonal analysis of pMN cells in zebrafish showed that some produce a primary motoneuron and KA' interneuron at their final division. We investigated the possibility that Notch signaling regulates a motoneuron-interneuron fate decision using a combination of mutant, transgenic and pharmacological manipulations of Notch activity. We show that continuous absence of Notch activity produces excess primary motoneurons and a deficit of KA' interneurons, whereas transient inactivation preceding neurogenesis results in an excess of both cell types. By contrast, activation of Notch signaling at the neural plate stage produces excess KA' interneurons and a deficit of primary motoneurons. Furthermore, individual pMN cells produce similar kinds of neurons at their final division in mib mutant embryos, which lack Notch signaling. These data provide evidence that, among some postmitotic daughters of pMN cells, Notch promotes KA' interneuron identity and inhibits primary motoneuron fate, raising the possibility that Notch signaling diversifies vertebrate neuron type by mediating similar binary fate decisions.
"Islet1 knock-down reduces Rohon-Beard cell number and expression of scn8aa in the dorsal spinal cord. (A-C) In 24 hours post-fertilization (hpf) Tg(scn8aa:gfp)ym1 embryos, Rohon-Beard (RB) and RB-like cells express green fluorescent protein (GFP) (dorsal views). Islet1 knock-down reduces the number of GFP+ neurons (C versus A and B). "
[Show abstract][Hide abstract] ABSTRACT: Background
In the spinal cord, stereotypic patterns of transcription factor expression uniquely identify neuronal subtypes. These transcription factors function combinatorially to regulate gene expression. Consequently, a single transcription factor may regulate divergent development programs by participation in different combinatorial codes. One such factor, the LIM-homeodomain transcription factor Islet1, is expressed in the vertebrate spinal cord. In mouse, chick and zebrafish, motor and sensory neurons require Islet1 for specification of biochemical and morphological signatures. Little is known, however, about the role that Islet1 might play for development of electrical membrane properties in vertebrates. Here we test for a role of Islet1 in differentiation of excitable membrane properties of zebrafish spinal neurons.
We focus our studies on the role of Islet1 in two populations of early born zebrafish spinal neurons: ventral caudal primary motor neurons (CaPs) and dorsal sensory Rohon-Beard cells (RBs). We take advantage of transgenic lines that express green fluorescent protein (GFP) to identify CaPs, RBs and several classes of interneurons for electrophysiological study. Upon knock-down of Islet1, cells occupying CaP-like and RB-like positions continue to express GFP. With respect to voltage-dependent currents, CaP-like and RB-like neurons have novel repertoires that distinguish them from control CaPs and RBs, and, in some respects, resemble those of neighboring interneurons. The action potentials fired by CaP-like and RB-like neurons also have significantly different properties compared to those elicited from control CaPs and RBs.
Overall, our findings suggest that, for both ventral motor and dorsal sensory neurons, Islet1 directs differentiation programs that ultimately specify electrical membrane as well as morphological properties that act together to sculpt neuron identity.
Neural Development 08/2014; 9(1):19. DOI:10.1186/1749-8104-9-19 · 3.45 Impact Factor
"identity -rather than solely the birthdate of habenular neurons. Indeed, a role of Notch in neuronal specification is already well described in other developmental contexts and organisms: for instance, in zebrafish, Notch signalling is required for the specification of projection neurons versus photoreceptors in the epiphysis (Cau et al., 2008) and for various neuronal subtypes in the ventral spinal cord (Shin et al., 2007). Consistent with a possible role of Notch in the direct specification of different habenular neuronal subtypes is the intriguing observation that in certain gain of Notch function "
[Show abstract][Hide abstract] ABSTRACT: How does left-right asymmetry develop in the brain and how does the resultant asymmetric circuitry impact on brain function and lateralized behaviors? By enabling scientists to address these questions at the levels of genes, neurons, circuitry and behavior,the zebrafish model system provides a route to resolve the complexity of brain lateralization. In this review, we present the progress made towards characterizing the nature of the gene networks and the sequence of morphogenetic events involved in the asymmetric development of zebrafish epithalamus. In an attempt to integrate the recent extensive knowledge into a working model and to identify the future challenges,we discuss how insights gained at a cellular/developmental level can be linked to the data obtained at a molecular/genetic level. Finally, we present some evolutionary thoughts and discuss how significant discoveries made in zebrafish should provide entry points to better understand the evolutionary origins of brain lateralization.
" differentiation ( Fortini and Artavanis - Tsakonas , 1993 ; Nye et al . , 1994 ; Louvi and Artavanis - Tsakonas , 2006 ) . Also during zebrafish embryonic neurogenesis , Notch sig - naling is involved in fate decision mechanism of neu - ral progenitors ( Jiang et al . , 1996 ; Haddon et al . , 1998 ; Takke et al . , 1999 ; Park and Appel , 2003 ; Shin et al . , 2007 ; Tallafuss et al . , 2009 ) . A recent study examined the role of Notch in adult neurogenesis of the zebrafish telencephalon and sug - gested that the presence of Notch signaling is associ - ated with keeping the progenitor cells quiescent ( Cha - pouton et al . , 2010 ) . High levels of Notch signaling activity has been suggested to b"
[Show abstract][Hide abstract] ABSTRACT: Adult neurogenesis is a widespread trait of vertebrates; however, the degree of this ability and the underlying activity of the adult neural stem cells differ vastly among species. In contrast to mammals that have limited neurogenesis in their adult brains,zebrafish can constitutively produce new neurons along the whole rostrocaudal brain axis throughout its life.This feature of adult zebrafish brain relies on the presence of stem/progenitor cells that continuously proliferate,and the permissive environment of zebrafish brain for neurogenesis. Zebrafish has also an extensive regenerative capacity, which manifests itself in responding to central nervous system injuries by producing new neurons to replenish the lost ones. This ability makes zebrafish a useful model organism for understanding the stem cell activity in the brain, and the molecular programs required for central nervous system regeneration.In this review, we will discuss the current knowledge on the stem cell niches, the characteristics of the stem/progenitor cells, how they are regulated and their involvement in the regeneration response of the adult zebrafish brain. We will also emphasize the open questions that may help guide the future research.
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