Neurogenesis of the basal forebrain in euploid and trisomy 16 mice: an animal model for developmental disorders in Down syndrome.
The neurogenesis and early histochemical differentiation of the basal forebrain in trisomy 16 fetal mice and their euploid littermates were examined by combining [3H]thymidine autoradiography with acetylcholinesterase histochemistry. Neurons of the basal forebrain were being born between embryonic day 11 and 15 in both chromosomally normal (euploid) and aneuploid mice. In euploid littermate controls, neurogenesis proceeded along a caudal to rostral gradient with the peak on embryonic day 11 for caudal portions and embryonic day 13 for rostral portions of the basal forebrain. In contrast, in trisomy 16 mice, rostral sections exhibited a peak of neurogenesis on embryonic day 11, 2 days earlier than in their euploid littermate controls. Hypocellularity of the basal forebrain region was noted in trisomy 16 mice; particularly dramatic was the reduction of the population of cells that expressed acetylcholinesterase. This reduction in cell number in the trisomics was not accompanied by a reduction in cell size or by a dramatic change in the distribution of residual neurons when compared to that of euploid littermate controls. Since trisomy 16 mice do not survive the perinatal period, we examined the pattern of acetylcholinesterase expression in normal C57B1/6J mice from embryonic day 16 to postnatal day 5 to determine the postnatal disposition of these neurons. Already at embryonic day 16, fibers staining for acetylcholinesterase penetrated the striatal anlage, in their course towards targets in the cerebral cortices. By postnatal day 5, the previously expansive distribution of basal forebrain neurons had become consolidated in a more ventral and rostral position by the extensive outgrowth of the striatal neurons, a pattern resembling that seen in adult animals.
Sweeney
J E
JE
Department of Environmental Health Sciences, Johns Hopkins University Medical Institutions, Baltimore, MD 21205.
Höhmann
C F
CF
Oster-Granite
M L
ML
Coyle
J T
JT
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002799:Cholinergic Fibers / Q000378:metabolism*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000196:embryology* / Q000473:pathology; D005314:Embryonic and Fetal Development; D005625:Frontal Lobe / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013936:Thymidine
D000110:Acetylcholinesterase; D013936:Thymidine