L-Maf, a downstream target of Pax6, is essential for chick lens development.
During lens development in vertebrates, the orchestration of multiple transcriptional regulators is essential for fate determination and terminal differentiation. In early development, Pax6, Sox2 and Six3 are expressed in the head ectoderm, while L-maf, Prox1 and crystallin genes are expressed at a later stage in the lens placode in a more restricted fashion. To uncover the genetic interactions among these factors during lens development, we examined the effects of dominant-negative molecules of Pax6 and L-Maf, which play decisive roles in lens formation. The two dominant-negative isoforms of Pax6 repress L-maf, Prox1 and delta-crystallin expression, resulting in failure of lens formation. These effects of dominant-negative Pax6 are fully rescued by co-expression with wild-type L-Maf. In addition, dominant-negative L-Maf inhibits the expression of Prox1 and delta-crystallin, while misexpression of L-Maf causes ectopic induction of these genes in a Sox-2-dependent fashion. Our results demonstrate that L-Maf is a downstream target of Pax6 and mediates Pax6 activity in developing lens cells.
Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma 630-0101, Japan.
Hasan Mahmud
HM
Reza
Hajime
H
Ogino
Kunio
K
Yasuda
D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D024002:HMGB Proteins; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007908:Lens, Crystalline / Q000196:embryology* / Q000378:metabolism; D050977:Maf Transcription Factors; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins; D038207:delta-Crystallins / Q000235:genetics / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C063459:En protein, Drosophila; D005136:Eye Proteins; D024002:HMGB Proteins; D018398:Homeodomain Proteins; C111440:L-MAF protein, Gallus gallus; D050977:Maf Transcription Factors; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D038207:delta-Crystallins; D000098551:Prospero-Related Homeobox 1 Protein