Mesencephalic Trigeminal Nucleus Development Is Dependent on Krox-20 Expression

Abstract

Krox-20, a C₂H₂-type zinc-finger transcription factor, plays an important role in rhombomere development. This study reveals that the Krox-20 null mutation impacts the development of mesencephalic trigeminal (Me5) neurons, a cell group traditionally thought to emerge from the mesencephalon. Based on cell counting studies, we show that Krox-20 null mutants have twice as many Me5 neurons relative to wildtypes at E15, but by birth have half the number of Me5 cells as wildtypes. TUNEL studies reveal a period of increased apoptosis from E17-P0 in mutants. The mutation does not result in differences in Me5 cell size, morphology, gene expression or peripheral projection patterns between genotypes, as demonstrated by retrograde tracing and Brn3a immunohistochemistry. The data suggest that Krox-20 regulates the period and extent of Me5 apoptosis, impacting the final number of Me5 neurons. The loss of Me5 in Krox-20^–/– mice may highlight species-specific differences in the origin of these cells.

Emergence of the sensory nervous system as defined by Foxs1 expression

“…The localization of the Foxs1 + cells in the mesencephalon is similar to the described anatomical location for the sensory mesencephalic trigeminal nuclei (mesV) neurons (Hunter et al, 2001). To determine the cellular identity of the Foxs1 + cells, serial sections were stained to detect Foxs1 expression along with Brn3a, which previously has been shown to specifically mark mesV nucleus neurons in the central nervous system at early stages (Hunter et al, 2001; De et al, 2005). All Foxs1 + cells of the mesencephalon double stained for Brn3a, although many Brn3a + cells were not Foxs1 + (Fig.…”

Development of the mesencephalic trigeminal nucleus requires a paired homeodomain transcription factor, Drg11

“…Brn3a, a member of the POU family of transcription factors, is expressed in the Me5, and Me5 neurons are lost in Brn3a −/− mice at postnatal day 0 (P0) (Xiang et al, 1996;Ichikawa et al, 2005). Krox-20, a C2H2-type zinc-finger transcription factor, impacts the final number of Me5 neurons by regulating the period and extent of apoptosis in the Me5 during development (De et al, 2005). In addition, the number of Me5 neurons is significantly reduced in trkC −/− mice, indicating that NT-3/trkC signaling is required for the survival of most Me5 neurons (Matsuo et al, 2000).…”