Foxg1 Regulates The Patterning And Regionalization Of The Dorsal Telencephalon

The early event of embryonic patternning is to establishhighly ordered anterior-posterior axis,medial-lateral axis and dorsal-ventral axeis under the control of numerous signal molecules.Currently,four major signal centers have been identified to be critical in telencephalon patternning.The One is Fgf signal center,located in the most rostral region of the developing telencephalon.The second is the cortical hem in which Wnt and Bmp signals are riched.The third is the anti-hem.The fourthis the POA located in the most ventral area of the developing telencephalon,from which Sonic Hedgehog(Shh)was secreted.These signaling centers define the telencephalon axes through secreting numerous of signal molecules.The regionalization of the telencephalon refers to theestablishment of functional areas.The functional areas of the telencephalon include somatosensory(S1),motor(M1).auditory area(A1)and visual(V1)area.It has been reported that the transcription factors EMX2,Pax6,COUP-TFI and Sp8 are important for controllingthe regionalization.However the mechanism underlying the pattern formation and regionalization remains unclear.The transcriptional factor foxgl,highly expressed in the telencephalon,plays essential roles in the development of nervous system.It has been reported that patients carrying mutations in foxgl suffer from mood disorder,cognitive abnormality and clinical manifestations include microcephalus.Previous studies have shownserious abnormalities of the pallium and the loss of subpalliun in foxg1-/-mice.Detailed analysis was unachievable due to embryonic death of foxg1-/-mice.Here EMX1-cre was employed to conditional disrupt foxgl in the telencephalic pallium from E10.5 to explore its role during the pattern formation and regionalization of telencephalon.We found that conditional knockout the foxgl led to the telencephalon severe decreased in size.1The hippocampus expanded dorsalaterally,the neocortex is almost completely missing;2 The pallium-subpallium boundary(PSB)shifted towards to the ventral telencephalon;3 The piriform cortex moved dorsolaterally together with a rostrallymoved olfactory tubercle;4 The ventral striatum became larger;5 The number of Reelin-positive Cajal-Rezius cells(CR)in dorsal cortex was increased and ectopically distributed in the dorsalventral cortex.To further elucidate the molecular mechanisms,we then examined the signal centers and its secreted molecules.Wnt3a,Wnt2b,Lefl showed no significant change,Wnt8b was up-regulated significantly,BMP4 was up-regulated.No obvious changes of Fgf8 and Shh were observed.The regional of Sfrp2 expressed moved ventrally.Interestingly we found some transcriptional factors which are important for regionalization were abnormal.In summary,our results suggested that foxgl plays an essential roles in the pattern formation and regionalization of the developing telencephalon,foxgl may located in the upstream of the important molecules of Hem,Anti-Hem and some transcriptional factors to promote the telencephalon pattern formation and regionalization.