Spinal ganglia reduction in the splotch‐delayed mouse neural tube defect mutant

Abstract

Splotch and splotch-delayed mutants have anomalies in certain neural crest cell derivatives as well as neural tube defects. A genetic marker was used to identify mutant, heterozygote, and wild-type embryos within a litter, which enabled us to make intergenotypic comparisons. Histological studies of the lumbosacral region of day 15 and day 16 embryos indicated that the splotch-delayed mutant had similar but less severe defects in spinal ganglion development than those reported for splotch (Auerbach: Journal of Experimental Zoology 127:305-329, 1954). The ganglia were extensively reduced in size, residual, or missing in the splotch-delayed mutant, whereas in the splotch mutant, they were virtually nonexistent. Paired comparison analyses showed that all mutant embryos had a significant reduction in their volume of lumbosacral spinal ganglia when compared to their heterozygous and/or wild-type littermates. Also, some heterozygotes were found to have spinal ganglia volumes that were significantly reduced when compared to wild-type embryos. The volume of spinal ganglia was not related to the severity of the neural tube defect. In fact, three mutant embryos, which did not exhibit a neural tube defect, had spinal ganglia volumes comparable to or less than those mutants with open neural tube lesions or curly tails. This shows that the formation of abnormal neural crest cell derivatives is not a result of the neural tube closure defect. We hypothesize that the two anomalies observed in these mutants have a common etiological basis.

Onset of ETS expression is not accelerated by premature exposure to signals from limb mesenchyme

“…Pea3 in mutant embryos, however, was less robust than in littermate controls, suggesting that, although the mesenchyme can initiate Pea3 expression, as previously reported (Helmbacher et al, 2003), myogenic cells are required for full expression and/or maintenance of Pea3 transcripts. As expected (Moase and Trasler, 1989), DRGs were reduced in size and/or misplaced in Sp d embryos. Nevertheless, both Er81 and Pea3 were expressed in some sensory neurons in mutant embryos (Fig.…”

Signals from the notochord and floor plate regulate the region-specific expression of two Pax genes in the developing spinal cord

“…The peripheral nervous system in the trunk region is severely affected. In Sp heterozygotes and Sp d homozygotes, dorsal root ganglia are smaller in size and, in Sp homozygotes, they are often completely absent (Auerbach, 1954;Moase and Trasler, 1989). The defects observed in the spinal cord and peripheral nervous system of splotch mice suggests Pax-3 plays a role in spinal cord development.…”

Understanding the causes and prevention of neural tube defects: Insights from the splotch mouse model

“…Less variation is observed for spinal NTDs, spina bifida being reported to occur in 85 to 100% of homozygotes for both the Sp or Sp 2H alleles (Auerbach, 1954;Copp 1998, 2000;Gefrides et al, 2002;Martin et al, 2003), although lower rates have been reported on specific genetic backgrounds (Moase and Trasler, 1987). In some studies, occasional spina bifida is also reported in heterozygotes (Moase and Trasler, 1989;Martin et al, 2003;Li et al, 2006).…”