Loss of Msx2 function down-regulates the FoxE3 expression and results in anterior segment dysgenesis resembling peters anomaly

Jiangyue Zhao, Kirio Kawai, Hongyan Wang, Di Wu, Mingwu Wang, Zhicao Yue, Jinsong Zhang, Yi Hsin Liu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Complex molecular interactions dictate the developmental steps that lead to a mature and functional cornea and lens. Peters anomaly is one subtype of anterior segment dysgenesis especially due to abnormal development of the cornea and lens. MSX2 was recently implicated as a potential gene that is critical for anterior segment development. However, the role of MSX2 within the complex mechanisms of eye development remains elusive. Our present study observed the morphologic changes in conventional Msx2 knockout (KO) mice and found phenotypes consistent with Peters anomaly and microphthalmia seen in humans. The role of Msx2 in cornea and lens development was further investigated using IHC, in situ hybridization, and quantification of proliferative and apoptotic lens cells. Loss of Msx2 down-regulated FoxE3 expression and up-regulated Prox1 and crystallin expression in the lens. The FoxE3 and Prox1 malfunction and precocious Prox1 and crystallin expression contribute to a disturbed lens cell cycle in lens vesicles and eventually to cornea-lentoid adhesions and microphthalmia in Msx2 KO mice. The observed changes in the expression of FoxE3 suggest that Msx2 is an important contributor in controlling transcription of target genes critical for early eye development. These results provide the first direct genetic evidence of the involvement of MSX2 in Peters anomaly and the distinct function of MSX2 in regulating the growth and development of lens vesicles.

Original languageEnglish (US)
Pages (from-to)2230-2239
Number of pages10
JournalAmerican Journal of Pathology
Volume180
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Lenses
Down-Regulation
Cornea
Microphthalmos
Crystallins
Knockout Mice
Peters anomaly
Growth and Development
Genes
In Situ Hybridization
Cell Cycle
Phenotype

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Loss of Msx2 function down-regulates the FoxE3 expression and results in anterior segment dysgenesis resembling peters anomaly. / Zhao, Jiangyue; Kawai, Kirio; Wang, Hongyan; Wu, Di; Wang, Mingwu; Yue, Zhicao; Zhang, Jinsong; Liu, Yi Hsin.

In: American Journal of Pathology, Vol. 180, No. 6, 06.2012, p. 2230-2239.

Research output: Contribution to journalArticle

Zhao, Jiangyue ; Kawai, Kirio ; Wang, Hongyan ; Wu, Di ; Wang, Mingwu ; Yue, Zhicao ; Zhang, Jinsong ; Liu, Yi Hsin. / Loss of Msx2 function down-regulates the FoxE3 expression and results in anterior segment dysgenesis resembling peters anomaly. In: American Journal of Pathology. 2012 ; Vol. 180, No. 6. pp. 2230-2239.
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