Pax-3 regulates neurogenesis in neural crest-derived precursor cells

Abstract

The peripheral nervous system consists of multiple neural lineages derived from the neural crest (NC). Pax-3 is expressed in the NC and when mutated in the splotch mouse (Sp) results in the loss of derivatives from this precursor cell population. We have investigated the role of Pax-3 in regulating the generation of neurons from NC-derived precursor cells in vitro. Pax-3 mRNA in NC cultures is initially expressed in all NC but is subsequently only retained in neurons, suggesting a role in their generation. To determine whether Pax-3 is involved in neuron development, we first examined the generation of sensory-like neurons in NC cultures from Sp mice. Fivefold less sensory-like neurons were generated in NC cultures from Sp homozygous mice as compared to wild-type littermates. The role of Pax-3 in sensory neuron generation was then directly examined in dorsal root ganglia cultures by down-regulating the expression of Pax-3 protein with antisense oligonucleotides. It was found that antisense oligonucleotides inhibited 80-90% of newly generated sensory neurons; however, there was no significant effect on the survival of sensory neurons or the precursor population. These results suggest that Pax-3 has a role in regulating the differentiation of peripheral neurons.

Wnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow

“…Id2 overexpression results in overgrowth and premature neurogenesis of the dorsal neural tube [22]. There is some evidence for Pax3 involvement in regulating sensory neurogenesis in trunk NCC [23]. Likewise, Pax6 has been shown to play an important role promoting neurogenesis.…”

The curly tail mouse model of human neural tube defects demonstrates normal spinal cord differentiation at the level of the meningomyelocele: implications for fetal surgery

“…This gene is a member of the paired box family of genes and is involved in patterning the dorsal neural tube. In addition to meningomyelocele, splotch mutants have defects of neural crest-derived tissues [6,12,19]. In humans, mutations of Pax3 result in Waardenburg syndrome type I (WS-I), in which NTD has been described [23].…”

Pax3 induces differentiation of juvenile skeletal muscle stem cells without transcriptional upregulation of canonical myogenic regulatory factors

“…They further are divided into four subfamilies based on their structural and expression domains (Gruss and Walther, 1992). The Pax3/7 subfamily regulates both myogenesis (Buckingham and Relaix, 2007) and neurogenesis in the neural crest (Koblar et al, 1999).…”