Spatial and temporal regulation of ventral spinal cord precursor specification by Hedgehog signaling

Abstract

Graded Hedgehog (Hh) signaling patterns the spinal cord dorsoventral axis by inducing and positioning distinct precursor domains, each of which gives rise to a different type of neuron. These domains also generate glial cells, but the full range of cell types that any one precursor population produces and the mechanisms that diversify cell fate are unknown. By fate mapping and clonal analysis in zebrafish, we show that individual ventral precursor cells that express olig2 can form motoneurons, interneurons and oligodendrocytes. However, olig2 + precursors are not developmentally equivalent, but instead produce subsets of progeny cells in a spatially and temporally biased manner.Using genetic and pharmacological manipulations, we provide evidence that these biases emerge from Hh acting over time to set, maintain, subdivide and enlarge the olig2 + precursor domain and subsequently specify oligodendrocyte development. Our studies show that spatial and temporal differences in Hh signaling within a common population of neural precursors can contribute to cell fate diversification.

Acetyl l-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos

“…The transcription factor hb9 is found in developing motor neurons of both mammals (William et al, 2003) and zebrafish (Cheesman et al, 2004;Park et al, 2004). In the hb9-GFP transgenic fish, motor neurons are labeled with strong neuron-specific expression of GFP under the control of the regulatory elements of the zebrafish hb9 gene (Flanagan-Steet et al, 2005;Nakano et al, 2005).…”

“…Importantly, in another study we also showed that acetyl L-carnitine counteracts ketamine's negative effects on heart rate and ERK (MAPK) activity in zebrafish embryos (Kanungo et al, 2012). In order to quantitate the effect of ketamine on motor neurons in vivo, hb9:green fluorescent protein (hb9:GFP) transgenic zebrafish embryos were used, in which the promoter of the transcription factor hb9 that is found in developing motor neurons of both mammals (William et al, 2003) and zebrafish (Cheesman et al, 2004;Park et al, 2004), drives GFP expression specifically in motor neurons (Flanagan-Steet et al, 2005;Nakano et al, 2005).…”

Neurogenic Role of the Depolarizing Chloride Gradient Revealed by Global Overexpression of KCC2 from the Onset of Development

“…We therefore looked at glial cells, the alternate fate most likely adopted by the precursors (Park et al, 2004), expecting a dramatic increase in this population. Because astrocytes are found only in adult zebrafish (Lewis and Eisen, 2003), we focused on radial glia and oligodendrocyte precursors, both found in the embryo (Appel et al, 2001;Park et al, 2002).…”

Ventral Neural Progenitors Switch toward an Oligodendroglial Fate in Response to Increased Sonic Hedgehog (Shh) Activity: Involvement of Sulfatase 1 in Modulating Shh Signaling in the Ventral Spinal Cord

“…As is the case for MNs, the emergence of ventral spinal cord OLPs was shown to be mostly dependent on induction involving local activity of Shh produced by floor plate cells (Poncet et al, 1996;Pringle et al, 1996;Soula et al, 2001;Agius et al, 2004;Park et al, 2004). The fact that Shh signaling is required to specify OLP, at a time long after dorsoventral neuronal patterning is completed (Orentas et al, 1999;Soula et al, 2001;Agius et al, 2004;Park et al, 2004), raises the question of how a single signaling molecule can confer chronologically distinct identities on the same set of ventral neural progenitors.…”