Determining the Role of neurogenin1 in the Development of the Mouse Dorsal Root Ganglion

Abstract

Neurogenin1 (ngn1) is required for the development of one sub‐type of neuron in the dorsal root ganglion (DRG) since ngn1 knockout mice specifically lack nociceptive neurons. This shows that ngn1 is required for neural development but does not indicate whether it is involved in neural vs. glial fate determination in nociceptive progenitors or if it participates in neural sub‐type specification. Because an analogous gene in the olfactory system (mash1) plays a role in neural fate determination, we hypothesize that ngn1 functions in neural vs. glial fate determination in the DRG. To test this hypothesis, we compared the expression of known cell‐type specific markers to determine the developmental fate of cells in the absence of ngn1 function. If ngn1 is involved in neural fate determination we expected to see a decrease in the proportion of nociceptors and an increase in the proportion of glial cells in the knockout mice relative to their wild‐type littermates. Gene expression was analyzed on transverse tissue sections from embryonic day (E) 10‐12.5 as this encompasses the onset of ngn1 expression in the DRG and the peak of DRG neurogenesis. We performed in situ hybridization using cell‐type specific probes to detect neural crest progenitor cells, sensory neuron sub‐types, and glial cells. Our current data is consistent with ngn1 functioning in neural fate determination as we have observed a specific decrease in trkA‐expressing nociceptors (trkB‐ and trkC‐expressing neurons are not affected) and an increase in the expression of sox10 (progenitors and glial cells) and fabp7 (glial cells) in the DRG of ngn1 knockout mice. Supported by grants from NCRR (P20RR016460) and NIGMS (P20 GM103429) at NIH.