Balanced Shh signaling is required for proper formation and maintenance of dorsal telencephalic midline structures.
BACKGROUND
The rostral telencephalic dorsal midline is an organizing center critical for the formation of the future cortex and hippocampus. While the intersection of WNTs, BMPs, and FGFs establishes boundaries within this critical center, a direct role of Shh signaling in this region remains controversial. In this paper we show that both increased and decreased Shh signaling directly affects boundary formation within the telencephalic dorsal midline.


RESULTS
Viral over-expression of Shh in the embryonic telencephalon prevents formation of the cortical hem and choroid plexus, while expanding the roof plate. In a transgenic model where cholesterol-lacking ShhN is expressed from one allele (ShhN/+), genes expressed in all three domains, cortical hem, choroid plexus and roof plate expand. In Gli1/2 -/- mutant brains, where Shh signaling is reduced, the roof plate expands, again at the expense of cortical hem and plexus. Cell autonomous activation of Shh signaling in the dorsal midline through Gdf7-driven activated Smoothened expression results in expansion of the Wnt3a-expressing cortical hem into the plexus domain. In addition, developmental stage determines dorsal midline responsiveness to Shh.


CONCLUSIONS
Together, these data demonstrate that balanced Shh signaling is critical for maintaining regional boundaries within the dorsal midline telencephalic organizing center.
Developmental Biology and Department of Pediatrics, Children's Memorial Research Center and Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Diana S
DS
Himmelstein
Chunming
C
Bi
Brian S
BS
Clark
Brian
B
Bai
Jhumku D
JD
Kohtz
D000818:Animals; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015398:Signal Transduction; D013687:Telencephalon / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C102995:Lhx5 protein, mouse; D009419:Nerve Tissue Proteins; C465570:Shh protein, mouse; D014157:Transcription Factors