Patterning of the lateral ganglionic eminence by the Gsh1 and Gsh2 homeobox genes regulates striatal and olfactory bulb histogenesis and the growth of axons through the basal ganglia

• Published in: Journal of comparative neurology (1911) 2003-06, Vol.461 (2), p.151-165
• Main Authors: Yun, Kyuson, Garel, Sonia, Fischman, Seth, Rubenstein, John L.R.
• Format: Article
• Language: English
• Subjects: Afferent Pathways - abnormalities; Afferent Pathways - cytology; Afferent Pathways - metabolism; Animals; Biomarkers; Body Patterning - genetics; Cell Movement - genetics; Cerebral Cortex - abnormalities; Cerebral Cortex - cytology; Cerebral Cortex - metabolism; Choristoma - genetics; Choristoma - metabolism; CNS development; Corpus Striatum - abnormalities; Corpus Striatum - cytology; Corpus Striatum - metabolism; cortical axons; Dopamine - metabolism; dorsoventral patterning; Efferent Pathways - abnormalities; Efferent Pathways - cytology; Efferent Pathways - metabolism; Genes, Homeobox - genetics; Growth Cones - metabolism; Growth Cones - ultrastructure; Gsh1; Gsh2; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Interneurons - cytology; Interneurons - metabolism; LGE; Mice; Mice, Knockout; Mutation - genetics; Olfactory Bulb - abnormalities; Olfactory Bulb - cytology; Olfactory Bulb - metabolism; Receptors, Dopamine D2 - genetics; Stem Cells - cytology; Stem Cells - metabolism; striatum; telencephalon; ventral pallium
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.10685

The function of the Gsh1 and Gsh2 homeobox transcription factors during development of the mouse telencephalon was studied using loss of function mutations. No telencephalic phenotype was observed in Gsh1 mutants, whereas Gsh2 and Gsh1/2 mutants showed progressively more severe defects in development of neurons derived from the lateral ganglionic eminence (LGE). These defects arise from abnormal dorsoventral specification of LGE progenitor cells. Mice lacking both Gsh1 and Gsh2 have severe hypoplasia of the striatum, olfactory tubercle, and interneurons that migrate from the dorsal LGE to the olfactory bulb. In addition, Gsh function is linked to the development of telencephalic dopaminergic neurons. These observations show that Gsh1 and Gsh2 have early roles in defining the identity of LGE progenitor cells. As a result of the basal ganglia defects in the Gsh1/2 mutants, there are pallial heterotopia near the cortical/subcortical limit and defects in the pathfinding of corticofugal and thalamocortical fibers. These findings highlight the developmental interdependence of adjacent telencephalic structures. J. Comp. Neurol. 461:151–165, 2003. © 2003 Wiley‐Liss, Inc.