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Jeffrey M. Gross - One of the best experts on this subject based on the ideXlab platform.
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mitf family transcription factor function is required within cranial neural crest cells to promote Choroid Fissure closure
Development, 2020Co-Authors: Katie Sinagoga, Alessandra M Larimerpicciani, Stephanie M George, Samantha A Spencer, James A Lister, Jeffrey M. GrossAbstract:Background Patients with an acute ischemic stroke (AIS) due to large vessel occlusion often require transfer to an endovascular center for treatment. Objective To assess the effect of hospital transfer on outcomes after endovascular revascularization. Methods Outcomes of endovascular revascularization were compared between directly admitted and transferred patients using data from a national database and our own institution. Results 118 institutions within the database reported outcomes of 8533 inpatient admissions for endovascular treatment of AIS. Mortality rate (14.9% vs 18.6%; p=0.049) and mortality index (1.1 vs 1.6; p=0.048) were significantly lower among directly admitted patients than among transferred patients. Within our institutional cohort of 140 patients who underwent endovascular therapy, directly admitted patients had a significantly faster time to revascularization than transferred patients (277.4 vs 420.4 min; p≤0.0001). Among transferred patients, an increasing distance of transferred hospital to our home institution was associated with an increasing risk of mortality (unit OR=1.26, 95% CI 1.07 to 1.54; p=0.0061). Conclusions Outcomes of revascularization may improve with methods to identify patients with large vessel occlusion before hospital admission, thus increasing the likelihood of initial triage to a comprehensive stroke center for patients eligible for endovascular intervention.
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mitf family transcription factor function is required within cranial neural crest cells to promote Choroid Fissure closure
bioRxiv, 2019Co-Authors: Katie Sinagoga, Alessandra M Larimerpicciani, Stephanie M George, Samantha A Spencer, James A Lister, Jeffrey M. GrossAbstract:A critical step in eye development is closure of the Choroid Fissure (CF), a transient structure in the ventral optic cup through which vasculature enters the eye and ganglion cell axons exit. While many factors have been identified that function during CF closure, the molecular and cellular mechanisms mediating this process remain poorly understood. Failure of CF closure results in colobomas. Recently, MITF was shown to be mutated in a subset of human coloboma patients, but how MITF functions during CF closure is unknown. To address this question, zebrafish with mutations in mitfa and tfec, two members of the Mitf-family of transcription factors, were analyzed and their functions during CF closure determined. mitfa;tfec mutants possess severe colobomas and our data demonstrate that Mitf activity is required within cranial neural crest cells (cNCCs) to facilitate CF closure. In the absence of Mitf function, cNCC migration and localization in the optic cup are perturbed. These data shed light on the cellular mechanisms underlying colobomas in patients with MITF mutations and identify a novel role for Mitf function in cNCCs during CF closure. Summary StatementMitf-family transcription factors act within cranial neural crest cells to promote Choroid Fissure closure. Without Mitf-family function, cNCC localization and function in the CF is disrupted, thus contributing to colobomas.
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tet2-/-;tet3-/- retinal cells do not undergo terminal differentiation.
2017Co-Authors: Pawat Seritrakul, Jeffrey M. GrossAbstract:(A,F) HuC/D labels RGCs and amacrine cells (ACs), which are reduced in number and located only in the central region of the INL in tet2-/-;tet3-/- retinae (arrow). (B,G) tet2-/-;tet3-/- mutant retinae almost entirely lack zpr-1+ red/green cones (arrow); (C,D,H,I) possess few zpr-3+ rods (arrow), and of those that are zpr-3+, outer segments are severely attenuated or almost absent (arrow). (E,J) tet2-/-;tet3-/- retinae also possess few zrf-1+ Müller glia (arrows in wild-type). In all cases, marker+ cells are located in the central/ventral part of the retina. (K,P) Zn8 detects neurolin, a protein enriched on RGCs and the optic nerve (arrowhead in K). (L,Q) Zn8 staining reveals the optic nerve in the Choroid Fissure and optic chiasm (arrow) of wild-type embryos but not in tet2-/-;tet3-/- mutants. (M-N) isl2b:GFP transgenics express GFP in RGCs and PRs, clearly labeling the optic nerve in whole-mount and section views (arrowhead). (R,S) The tet2-/-;tet3-/- optic nerve is very thin, often unilaterally formed, but, when present, correctly routed to the brain. (O,T) The isl2b:GFP signal overlaps zpr-3 (rod) marker in the cell body and outer segments in siblings (arrows). In tet2-/-;tet3-/-, few isl2b:GFP+ cells are zpr-3+ (arrows), further suggesting that specified cells are not terminally differentiated. Few outer segments have also formed in tet2-/-;tet3-/- mutants. DNA (blue), antibody stain (red). All images are 3dpf. n>5 for each marker. Dorsal is up and anterior to the left. Scale bar = 80μm in A-K, P.
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Zebrafish blowout provides genetic evidence for Patched1 mediated negative regulation of Hedgehog signaling within the proximal optic vesicle of the vertebrate eye
Developmental biology, 2008Co-Authors: Jiwoon Lee, Jason R. Willer, Gregory B. Willer, Kierann Smith, Ronald G. Gregg, Jeffrey M. GrossAbstract:In this study, we have characterized the ocular defects in the recessive zebrafish mutant blowout that presents with a variably penetrant coloboma phenotype. blowout mutants develop unilateral or bilateral colobomas and as a result, the retina and retinal pigmented epithelium are not contained within the optic cup. Colobomas result from defects in optic stalk morphogenesis whereby the optic stalk extends into the retina and impedes the lateral edges of the Choroid Fissure from meeting and fusing. The expression domain of the proximal optic vesicle marker pax2a is expanded in blowout at the expense of the distal optic vesicle marker pax6, suggesting that the initial patterning of the optic vesicle into proximal and distal territories is disrupted in blowout. Later aspects of distal optic cup formation (i.e. retina development) are normal in blowout mutants, however. Positional cloning of blowout identified a nonsense mutation in patched1, a negative regulator of the Hedgehog pathway, as the underlying cause of the blowout phenotype. Expanded domains of expression of the Hedgehog target genes patched1 and patched2 were observed in blowout, consistent with a loss of Patched1 function and upregulation of Hedgehog pathway activity. Moreover, colobomas in blowout could be suppressed by pharmacologically inhibiting the Hedgehog pathway with cyclopamine, and maximal rescue occurred when embryos were exposed to cyclopamine between 5.5 and 13 hours post-fertilization. These observations highlight the critical role that Hedgehog pathway activity plays in mediating patterning of the proximal/distal axis of the optic vesicle during the early phases of eye development and they provide genetic confirmation for the integral role that patched1-mediated negative regulation of Hedgehog signaling plays during vertebrate eye development.
Stephen W. Wilson - One of the best experts on this subject based on the ideXlab platform.
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Cell Behaviors during Closure of the Choroid Fissure in the Developing Eye
Frontiers Media S.A., 2018Co-Authors: Gaia Gestri, Naiara Bazin-lopez, Clarissa Scholes, Stephen W. WilsonAbstract:Coloboma is a defect in the morphogenesis of the eye that is a consequence of failure of Choroid Fissure fusion. It is among the most common congenital defects in humans and can significantly impact vision. However, very little is known about the cellular mechanisms that regulate Choroid Fissure closure. Using high-resolution confocal imaging of the zebrafish optic cup, we find that apico-basal polarity is re-modeled in cells lining the Fissure in proximal to distal and inner to outer gradients during fusion. This process is accompanied by cell proliferation, displacement of vasculature, and contact between cells lining the Choroid Fissure and periocular mesenchyme (POM). To investigate the role of POM cells in closure of the Fissure, we transplanted optic vesicles onto the yolk, allowing them to develop in a situation where they are depleted of POM. The Choroid Fissure forms normally in ectopic eyes but fusion fails in this condition, despite timely apposition of the nasal and temporal lips of the retina. This study resolves some of the cell behaviors underlying Choroid Fissure fusion and supports a role for POM in Choroid Fissure fusion
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Video2.MOV
2018Co-Authors: Gaia Gestri, Naiara Bazin-lopez, Clarissa Scholes, Stephen W. WilsonAbstract:Coloboma is a defect in the morphogenesis of the eye that is a consequence of failure of Choroid Fissure fusion. It is among the most common congenital defects in humans and can significantly impact vision. However, very little is known about the cellular mechanisms that regulate Choroid Fissure closure. Using high-resolution confocal imaging of the zebrafish optic cup, we find that apico-basal polarity is re-modeled in cells lining the Fissure in proximal to distal and inner to outer gradients during fusion. This process is accompanied by cell proliferation, displacement of vasculature, and contact between cells lining the Choroid Fissure and periocular mesenchyme (POM). To investigate the role of POM cells in closure of the Fissure, we transplanted optic vesicles onto the yolk, allowing them to develop in a situation where they are depleted of POM. The Choroid Fissure forms normally in ectopic eyes but fusion fails in this condition, despite timely apposition of the nasal and temporal lips of the retina. This study resolves some of the cell behaviors underlying Choroid Fissure fusion and supports a role for POM in Choroid Fissure fusion.
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retinoic acid receptor signaling regulates Choroid Fissure closure through independent mechanisms in the ventral optic cup and periocular mesenchyme
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Giuseppe Lupo, Roshantha A S Chandraratna, Gaia Gestri, Matthew Obrien, Ross M Denton, Steven V Ley, William A Harris, Stephen W. WilsonAbstract:Retinoic acid receptor (RAR) signaling is required for morphogenesis of the ventral optic cup and closure of the Choroid Fissure, but the mechanisms by which this pathway regulates ventral eye development remain controversial and poorly understood. Although previous studies have implicated neural crest-derived periocular mesenchyme (POM) as the critical target of RA action in the eye, we show here that RAR signaling regulates Choroid Fissure closure in zebrafish by acting on both the ventral optic cup and the POM. We describe RAR-dependent regulation of eight genes in the neuroepithelial cells of the ventral retina and optic stalk and of six genes in the POM and show that these ventral retina/optic stalk and POM genes function independently of each other. Consequently, RAR signaling regulates ventral eye development through two independent, nonredundant mechanisms in different ocular tissues. Furthermore, the identification of two cohorts of genes implicated in ventral eye morphogenesis may help to elucidate the genetic basis of ocular coloboma in humans.
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Lmx1b is essential for survival of periocular mesenchymal cells and influences Fgf-mediated retinal patterning in zebrafish.
Developmental biology, 2009Co-Authors: Carrie Mcmahon, Gaia Gestri, Stephen W. Wilson, Brian A. LinkAbstract:To gain insight into the mechanisms of Lmx1b function during ocular morphogenesis, we have studied the roles of lmx1b.1 and lmx1b.2 during zebrafish eye development. In situ hybridization and characterization of transgenic lines in which GFP is expressed under lmx1b.1 regulatory sequence show that these genes are expressed in periocular tissues and in a pattern conserved with other vertebrates. Anti-sense morpholinos against lmx1b.1 and lmx1b.2 result in defective migration of periocular mesenchymal cells around the eye and lead to apoptosis of these cells. These defects in the periocular mesenchyme are correlated with a failure in fusion of the Choroid Fissure or in some instances, more severe ventral optic cup morphogenesis phenotypes. Indeed, by blocking the death of the periocular mesenchyme in Lmx1b morphants, optic vesicle morphogenesis is largely restored. Within the retina of lmx1b morphants, Fgf activity is transiently up-regulated and these morphants show defective naso-temporal patterning. Epistasis experiments indicate that the increase in Fgf activity is partially responsible for the ocular anomalies caused by loss of Lmx1b function. Overall, we propose zebrafish lmx1b.1 and lmx1b.2 promote the survival of periocular mesenchymal cells that influence multiple signaling events required for proper ocular development.
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hedgehog signalling maintains the optic stalk retinal interface through the regulation of vax gene activity
Development, 2003Co-Authors: Masaya Takeuchi, Jonathan D W Clarke, Stephen W. WilsonAbstract:During early formation of the eye, the optic vesicle becomes partitioned into a proximal domain that forms the optic nerve and a distal domain that forms the retina. In this study, we investigate the activity of Nodal, Hedgehog (Hh) and Fgf signals and Vax family homeodomain proteins in this patterning event. We show that zebrafish vax1 and vax2 are expressed in overlapping domains encompassing the ventral retina, optic stalks and preoptic area. Abrogation of Vax1 and Vax2 activity leads to a failure to close the Choroid Fissure and progressive expansion of retinal tissue into the optic nerve, finally resulting in a fusion of retinal neurons and pigment epithelium with forebrain tissue. We show that Hh signals acting through Smoothened act downstream of the Nodal pathway to promote Vax gene expression. However, in the absence of both Nodal and Hh signals, Vax genes are expressed revealing that other signals, which we show include Fgfs, contribute to Vax gene regulation. Finally, we show that Pax2.1 and Vax1/Vax2 are likely to act in parallel downstream of Hh activity and that the bel locus (yet to be cloned) mediates the ability of Hh-, and perhaps Fgf-, signals to induce Vax expression in the preoptic area. Taking all these results together, we present a model of the partitioning of the optic vesicle along its proximo-distal axis.
Katie Sinagoga - One of the best experts on this subject based on the ideXlab platform.
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mitf family transcription factor function is required within cranial neural crest cells to promote Choroid Fissure closure
Development, 2020Co-Authors: Katie Sinagoga, Alessandra M Larimerpicciani, Stephanie M George, Samantha A Spencer, James A Lister, Jeffrey M. GrossAbstract:Background Patients with an acute ischemic stroke (AIS) due to large vessel occlusion often require transfer to an endovascular center for treatment. Objective To assess the effect of hospital transfer on outcomes after endovascular revascularization. Methods Outcomes of endovascular revascularization were compared between directly admitted and transferred patients using data from a national database and our own institution. Results 118 institutions within the database reported outcomes of 8533 inpatient admissions for endovascular treatment of AIS. Mortality rate (14.9% vs 18.6%; p=0.049) and mortality index (1.1 vs 1.6; p=0.048) were significantly lower among directly admitted patients than among transferred patients. Within our institutional cohort of 140 patients who underwent endovascular therapy, directly admitted patients had a significantly faster time to revascularization than transferred patients (277.4 vs 420.4 min; p≤0.0001). Among transferred patients, an increasing distance of transferred hospital to our home institution was associated with an increasing risk of mortality (unit OR=1.26, 95% CI 1.07 to 1.54; p=0.0061). Conclusions Outcomes of revascularization may improve with methods to identify patients with large vessel occlusion before hospital admission, thus increasing the likelihood of initial triage to a comprehensive stroke center for patients eligible for endovascular intervention.
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mitf family transcription factor function is required within cranial neural crest cells to promote Choroid Fissure closure
bioRxiv, 2019Co-Authors: Katie Sinagoga, Alessandra M Larimerpicciani, Stephanie M George, Samantha A Spencer, James A Lister, Jeffrey M. GrossAbstract:A critical step in eye development is closure of the Choroid Fissure (CF), a transient structure in the ventral optic cup through which vasculature enters the eye and ganglion cell axons exit. While many factors have been identified that function during CF closure, the molecular and cellular mechanisms mediating this process remain poorly understood. Failure of CF closure results in colobomas. Recently, MITF was shown to be mutated in a subset of human coloboma patients, but how MITF functions during CF closure is unknown. To address this question, zebrafish with mutations in mitfa and tfec, two members of the Mitf-family of transcription factors, were analyzed and their functions during CF closure determined. mitfa;tfec mutants possess severe colobomas and our data demonstrate that Mitf activity is required within cranial neural crest cells (cNCCs) to facilitate CF closure. In the absence of Mitf function, cNCC migration and localization in the optic cup are perturbed. These data shed light on the cellular mechanisms underlying colobomas in patients with MITF mutations and identify a novel role for Mitf function in cNCCs during CF closure. Summary StatementMitf-family transcription factors act within cranial neural crest cells to promote Choroid Fissure closure. Without Mitf-family function, cNCC localization and function in the CF is disrupted, thus contributing to colobomas.
Teri L. Belecky-adams - One of the best experts on this subject based on the ideXlab platform.
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Ectopic Pax2 expression in chick ventral optic cup phenocopies loss of Pax2 expression.
Developmental Biology, 2008Co-Authors: R. Sehgal, Rachel E. Karcavich, Scott Carlson, Teri L. Belecky-adamsAbstract:Abstract Pax2 is essential for the development of the urogenital system, neural tube, otic vesicle, optic cup and optic tract [Dressler, G.R., Deutsch, U., et al., 1990. PAX2, a new murine paired-box-containing gene and its expression in the developing excretory system. Development 109 (4), 787–795; Nornes, H.O., Dressler, G.R., et al., 1990. Spatially and temporally restricted expression of Pax2 during murine neurogenesis. Development 109 (4), 797–809; Eccles, M.R., Wallis, L.J., et al., 1992. Expression of the PAX2 gene in human fetal kidney and Wilms’ tumor. Cell Growth Differ 3 (5), 279–289]. Within the visual system, a loss-of-function leads to lack of Choroid Fissure closure (known as a coloboma), a loss of optic nerve astrocytes, and anomalous axonal pathfinding at the optic chiasm [Favor, J., Sandulache, R., et al., 1996. The mouse Pax2(1Neu) mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye, and kidney. Proc. Natl. Acad. Sci. U. S. A. 93 (24), 13870–13875; Torres, M., Gomez-Pardo, E., et al., 1996. Pax2 contributes to inner ear patterning and optic nerve trajectory. Development 122 (11), 3381–3391]. This study is directed at determining the effects of ectopic Pax2 expression in the chick ventral optic cup past the normal developmental period when Pax2 is found. In ovo electroporation of Pax2 into the chick ventral optic cup results in the formation of colobomas, a condition typically associated with a loss of Pax2 expression. While the overexpression of Pax2 appears to phenocopy a loss of Pax2 , the mechanism of the failure of Choroid Fissure closure is associated with a cell fate switch from ventral retina and retinal pigmented epithelium (RPE) to an astrocyte fate. Further, ectopic expression of Pax2 in RPE appears to have non-cell autonomous effects on adjacent RPE, creating an ectopic neural retina in place of the RPE.
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Correlations between Terminal Mitosis and Differentiated Fate of Retinal Precursor Cellsin Vivoandin Vitro:Analysis with the “Window-Labeling” Technique
Developmental biology, 1996Co-Authors: Teri L. Belecky-adams, Briggs Cook, Ruben AdlerAbstract:We have investigated with high resolution the timing of retinal precursor cell commitment to specific differentiated fates, using anin ovomodification of thein vitro“window-labeling” technique (A. M. Repka and R. Adler,J. Histochem. Cytochem.40, 947–953, 1992a). The method involves an initial injection of tritiated thymidine into chick embryos, followed a specified number of hours later by an injection of bromodeoxyuridine (BrDU); cells born during this period are identified by being labeled with thymidine but not with BrDU. We used this method to determine, in a narrow region adjacent to the Choroid Fissure, the fate of cells born during defined 5-hr intervals between Embryonic Days (ED) 4–8. All the cohorts gave rise to heterogenous differentiated populations, indicating that time of cell birth is not a major cell fate determinant. A progressive restriction in the developmental potential of precursor cells, however, was suggested by the observed decrease in the number of different populations generated during each 5-hr period from ED 4 to 8, and supported also by dissociated cell culture experiments investigating the fate of cells born at different developmental stages. Microenvironmental influences were testedin vitrousing cells windowed-labeledin ovofor 5 hr on ED 5. After spending at least 72 hr within the retina before their isolation for culture, these cells mimicked theirin vivofate, giving rise predominantly to nonphotoreceptor neurons; a completely different behavior was observed when the cells were isolated after shorter exposures to the retinal microenvironment, when they gave rise predominantly to photoreceptors. Together with data demonstrating that differential cell death cannot account for these results, our results are consistent with the hypothesis that cell fate determination occurs after the time of terminal mitosis.
Gaia Gestri - One of the best experts on this subject based on the ideXlab platform.
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Cell Behaviors during Closure of the Choroid Fissure in the Developing Eye
Frontiers Media S.A., 2018Co-Authors: Gaia Gestri, Naiara Bazin-lopez, Clarissa Scholes, Stephen W. WilsonAbstract:Coloboma is a defect in the morphogenesis of the eye that is a consequence of failure of Choroid Fissure fusion. It is among the most common congenital defects in humans and can significantly impact vision. However, very little is known about the cellular mechanisms that regulate Choroid Fissure closure. Using high-resolution confocal imaging of the zebrafish optic cup, we find that apico-basal polarity is re-modeled in cells lining the Fissure in proximal to distal and inner to outer gradients during fusion. This process is accompanied by cell proliferation, displacement of vasculature, and contact between cells lining the Choroid Fissure and periocular mesenchyme (POM). To investigate the role of POM cells in closure of the Fissure, we transplanted optic vesicles onto the yolk, allowing them to develop in a situation where they are depleted of POM. The Choroid Fissure forms normally in ectopic eyes but fusion fails in this condition, despite timely apposition of the nasal and temporal lips of the retina. This study resolves some of the cell behaviors underlying Choroid Fissure fusion and supports a role for POM in Choroid Fissure fusion
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Video2.MOV
2018Co-Authors: Gaia Gestri, Naiara Bazin-lopez, Clarissa Scholes, Stephen W. WilsonAbstract:Coloboma is a defect in the morphogenesis of the eye that is a consequence of failure of Choroid Fissure fusion. It is among the most common congenital defects in humans and can significantly impact vision. However, very little is known about the cellular mechanisms that regulate Choroid Fissure closure. Using high-resolution confocal imaging of the zebrafish optic cup, we find that apico-basal polarity is re-modeled in cells lining the Fissure in proximal to distal and inner to outer gradients during fusion. This process is accompanied by cell proliferation, displacement of vasculature, and contact between cells lining the Choroid Fissure and periocular mesenchyme (POM). To investigate the role of POM cells in closure of the Fissure, we transplanted optic vesicles onto the yolk, allowing them to develop in a situation where they are depleted of POM. The Choroid Fissure forms normally in ectopic eyes but fusion fails in this condition, despite timely apposition of the nasal and temporal lips of the retina. This study resolves some of the cell behaviors underlying Choroid Fissure fusion and supports a role for POM in Choroid Fissure fusion.
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retinoic acid receptor signaling regulates Choroid Fissure closure through independent mechanisms in the ventral optic cup and periocular mesenchyme
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Giuseppe Lupo, Roshantha A S Chandraratna, Gaia Gestri, Matthew Obrien, Ross M Denton, Steven V Ley, William A Harris, Stephen W. WilsonAbstract:Retinoic acid receptor (RAR) signaling is required for morphogenesis of the ventral optic cup and closure of the Choroid Fissure, but the mechanisms by which this pathway regulates ventral eye development remain controversial and poorly understood. Although previous studies have implicated neural crest-derived periocular mesenchyme (POM) as the critical target of RA action in the eye, we show here that RAR signaling regulates Choroid Fissure closure in zebrafish by acting on both the ventral optic cup and the POM. We describe RAR-dependent regulation of eight genes in the neuroepithelial cells of the ventral retina and optic stalk and of six genes in the POM and show that these ventral retina/optic stalk and POM genes function independently of each other. Consequently, RAR signaling regulates ventral eye development through two independent, nonredundant mechanisms in different ocular tissues. Furthermore, the identification of two cohorts of genes implicated in ventral eye morphogenesis may help to elucidate the genetic basis of ocular coloboma in humans.
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Lmx1b is essential for survival of periocular mesenchymal cells and influences Fgf-mediated retinal patterning in zebrafish.
Developmental biology, 2009Co-Authors: Carrie Mcmahon, Gaia Gestri, Stephen W. Wilson, Brian A. LinkAbstract:To gain insight into the mechanisms of Lmx1b function during ocular morphogenesis, we have studied the roles of lmx1b.1 and lmx1b.2 during zebrafish eye development. In situ hybridization and characterization of transgenic lines in which GFP is expressed under lmx1b.1 regulatory sequence show that these genes are expressed in periocular tissues and in a pattern conserved with other vertebrates. Anti-sense morpholinos against lmx1b.1 and lmx1b.2 result in defective migration of periocular mesenchymal cells around the eye and lead to apoptosis of these cells. These defects in the periocular mesenchyme are correlated with a failure in fusion of the Choroid Fissure or in some instances, more severe ventral optic cup morphogenesis phenotypes. Indeed, by blocking the death of the periocular mesenchyme in Lmx1b morphants, optic vesicle morphogenesis is largely restored. Within the retina of lmx1b morphants, Fgf activity is transiently up-regulated and these morphants show defective naso-temporal patterning. Epistasis experiments indicate that the increase in Fgf activity is partially responsible for the ocular anomalies caused by loss of Lmx1b function. Overall, we propose zebrafish lmx1b.1 and lmx1b.2 promote the survival of periocular mesenchymal cells that influence multiple signaling events required for proper ocular development.