title: Multiple requirements for Hes 1 during early eye formation.
abstract: During embryogenesis, multiple developmental processes are integrated through their precise temporal regulation. Hes1 is a transcriptional repressor that regulates the timing of mammalian retinal neurogenesis. However, roles for Hes1 in early eye development have not been well defined. Here, we show that Hes1 is expressed in the forming lens, optic vesicle, cup, and pigmented epithelium and is necessary for proper growth, morphogenesis, and differentiation of these tissues. Because Hes1 is required throughout the eye, we investigated its interaction with Pax6. Hes1-Pax6 double mutant embryos are eyeless suggesting these genes are coordinately required for initial morphogenesis and outgrowth of the optic vesicle. In Hes1 mutants, Math5 expression is precocious along with retinal ganglion cell, amacrine, and horizontal neuron formation. In contrast to apparent cooperativity between Pax6 and Hes1 during morphogenesis, each gene regulates Math5 and RGC genesis independently. Together, these studies demonstrate that Hes1, like Pax6, simultaneously regulates multiple developmental processes during optic development.
authors.affiliation: Department of Pediatrics, Northwestern University Medical School at Children's Memorial Institute for Education and Research, Chicago, IL 60614, USA.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Emily
authors.initials: E
authors.lastname: Wroblewski
authors.forename: Gary T
authors.initials: GT
authors.lastname: Philips
authors.forename: Carrie N
authors.initials: CN
authors.lastname: Stair
authors.forename: Kevin
authors.initials: K
authors.lastname: Conley
authors.forename: Meredith
authors.initials: M
authors.lastname: Reedy
authors.forename: Grant S
authors.initials: GS
authors.lastname: Mastick
authors.forename: Nadean L
authors.initials: NL
authors.lastname: Brown
mesh_terms: D025042:Amacrine Cells / Q000166:cytology / Q000196:embryology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D047108:Embryonic Development; D004843:Epistasis, Genetic; D005123:Eye / Q000166:cytology / Q000196:embryology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007908:Lens, Crystalline / Q000166:cytology / Q000196:embryology; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000196:embryology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology; D012165:Retinal Ganglion Cells / Q000166:cytology; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C117638:Atoh7 protein, mouse; C489734:Hes1 protein, mouse; C000605732:Pax6 protein, mouse