Talk:Sensory - Vision Development

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Cite this page: Hill, M.A. (2021, October 22) Embryology Sensory - Vision Development. Retrieved from


Cytoskeleton proteins previously considered exclusive to Ganglion Cells are transiently expressed by all retinal neuronal precursors

BMC Dev Biol. 2011 Jul 22;11:46.

Gutierrez C, McNally M, Canto-Soler MV. Source Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD USA.

Abstract ABSTRACT:

BACKGROUND: Understanding the mechanisms governing cell fate specification remains one of the main challenges in the study of retinal development. In this context, molecular markers that identify specific cell types become crucial tools for the analysis and interpretation of these phenomena. In studies using the developing chick retina, expression of the mid-size neurofilament (NF-M) and a chick-specific microtubule associated protein recognized by the RA4 antibody (MAP(RA4)), have been broadly used to selectively identify ganglion cells and their committed precursors. However, observations in our laboratory suggested that the expression of these proteins may not be restricted to cells of the ganglion cell lineage. Because of its potential significance in the field, we pursued a detailed analysis of the expression of these two molecules in combination with an array of proteins that allowed precise identification of all retinal cell-type precursors throughout the development of the chick retina.

RESULTS: Both, NF-M and MAP(RA4) proteins, showed a dynamic pattern of expression coincident with the progression of retinal cell differentiation. Both proteins were coexpressed spatially and temporally in postmitotic neuronal precursors throughout development. Expression of both proteins was seen in ganglion cell precursors and adult differentiated ganglion cells, but they were also transiently expressed by precursors of the photoreceptor, horizontal, bipolar and amacrine cell lineages.

CONCLUSIONS: We have clearly demonstrated that, contrary to the generally accepted paradigm, expression of NF-M and MAP(RA4) proteins is not exclusive to ganglion cells. Rather, both proteins are transiently expressed by all neuronal retinal progenitors in a developmentally-regulated manner. In addition, MAP(RA4) and NF-M are the first molecules so far characterized that may allow unambiguous identification of postmitotic precursors from the pool of mitotically active progenitors and/or the differentiated cell population during retinogenesis. These results are of significant impact for the field of developmental biology of the retina, since they provide novel and important information for the appropriate design and interpretation of studies on retinal cell differentiation, as well as for the reinterpretation of previously published studies.

PMID 21781303

Neural crest cells organize the eye via TGF-β and canonical Wnt signalling

Nat Commun. 2011 Apr;2:265.

Grocott T, Johnson S, Bailey AP, Streit A. Source Department of Craniofacial Development, King's College London, Guy's Campus, London SE1 9RT, UK.


In vertebrates, the lens and retina arise from different embryonic tissues raising the question of how they are aligned to form a functional eye. Neural crest cells are crucial for this process: in their absence, ectopic lenses develop far from the retina. Here we show, using the chick as a model system, that neural crest-derived transforming growth factor-βs activate both Smad3 and canonical Wnt signalling in the adjacent ectoderm to position the lens next to the retina. They do so by controlling Pax6 activity: although Smad3 may inhibit Pax6 protein function, its sustained downregulation requires transcriptional repression by Wnt-initiated β-catenin. We propose that the same neural crest-dependent signalling mechanism is used repeatedly to integrate different components of the eye and suggest a general role for the neural crest in coordinating central and peripheral parts of the sensory nervous system.

PMID 21468017


Eye morphogenesis and patterning of the optic vesicle

Curr Top Dev Biol. 2010;93:61-84.

Fuhrmann S.

Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Abstract Organogenesis of the eye is a multistep process that starts with the formation of optic vesicles followed by invagination of the distal domain of the vesicles and the overlying lens placode resulting in morphogenesis of the optic cup. The late optic vesicle becomes patterned into distinct ocular tissues: the neural retina, retinal pigment epithelium (RPE), and optic stalk. Multiple congenital eye disorders, including anophthalmia or microphthalmia, aniridia, coloboma, and retinal dysplasia, stem from disruptions in embryonic eye development. Thus, it is critical to understand the mechanisms that lead to initial specification and differentiation of ocular tissues. An accumulating number of studies demonstrate that a complex interplay between inductive signals provided by tissue-tissue interactions and cell-intrinsic factors is critical to ensuring proper specification of ocular tissues as well as maintenance of RPE cell fate. While several of the extrinsic and intrinsic determinants have been identified, we are just at the beginning in understanding how these signals are integrated. In addition, we know very little about the actual output of these interactions. In this chapter, we provide an update of the mechanisms controlling the early steps of eye development in vertebrates, with emphasis on optic vesicle evagination, specification of neural retina and RPE at the optic vesicle stage, the process of invagination during morphogenesis of the optic cup, and maintenance of the RPE cell fate.

Copyright © 2010 Elsevier Inc. All rights reserved. PMID 20959163

Rearrangement of retinogeniculate projection patterns after eye-specific segregation in mice

Hayakawa I, Kawasaki H. PLoS One. 2010 Jun 8;5(6):e11001. PMID: 20544023


Generation of functional eyes from pluripotent cells

PLoS Biol. 2009 Aug;7(8):e1000174. Epub 2009 Aug 18.

Viczian AS, Solessio EC, Lyou Y, Zuber ME.

Department of Ophthalmology, State University of New York (SUNY) Upstate Medical University, Syracuse, New York, United States of America. Comment in:

PLoS Biol. 2009;7(8):e1000175. Abstract Pluripotent cells such as embryonic stem (ES) and induced pluripotent stem (iPS) cells are the starting point from which to generate organ specific cell types. For example, converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations. In this study, we used an in vivo strategy to determine if functional retinas could be generated from a defined population of pluripotent Xenopus laevis cells. Animal pole cells isolated from blastula stage embryos are pluripotent. Untreated, these cells formed only epidermis, when transplanted to either the flank or eye field. In contrast, misexpression of seven transcription factors induced the formation of retinal cell types. Induced retinal cells were committed to a retinal lineage as they formed eyes when transplanted to the flanks of developing embryos. When the endogenous eye field was replaced with induced retinal cells, they formed eyes that were molecularly, anatomically, and electrophysiologically similar to normal eyes. Importantly, induced eyes could guide a vision-based behavior. These results suggest the fate of pluripotent cells may be purposely altered to generate multipotent retinal progenitor cells, which differentiate into functional retinal cell classes and form a neural circuitry sufficient for vision.

PMID 19688031

Shaping the vertebrate eye

Martinez-Morales JR, Wittbrodt J. Curr Opin Genet Dev. 2009 Oct;19(5):511-7. Epub 2009 Oct 8. Review. For over a century, the vertebrate eye has served as a paradigm for organogenesis. It forms through a complex sequence of morphogenetic events, involving the lateral evagination of the optic vesicles and their subsequent folding into the optic cups. Through intensive studies by experimental embryologists, anatomical descriptions of the process were available since many decades. Recent genetic and molecular work has illuminated essential features of the stereotyped cellular behaviour driving eye morphogenesis. The first pieces of the molecular machinery operating in each individual progenitor cell have been identified. These studies now set the groundwork for a system-wide approach towards understanding the cellular and molecular mechanisms involved in shaping the vertebrate eye.

PMID 19819125

Progenitor cells of the rod-free area centralis originate in the anterior dorsal optic vesicle

Shin SK, O'Brien KM. BMC Dev Biol. 2009 Nov 25;9:57. PMID: 19939282


The other pigment cell: specification and development of the pigmented epithelium of the vertebrate eye

Bharti K, Nguyen MT, Skuntz S, Bertuzzi S, Arnheiter H. Pigment Cell Res. 2006 Oct;19(5):380-94. Review.

Vertebrate retinal pigment epithelium (RPE) cells are derived from the multipotent optic neuroepithelium, develop in close proximity to the retina, and are indispensible for eye organogenesis and vision. Recent advances in our understanding of RPE development provide evidence for how critical signaling factors operating in dorso-ventral and distal-proximal gradients interact with key transcription factors to specify three distinct domains in the budding optic neuroepithelium: the distal future retina, the proximal future optic stalk/optic nerve, and the dorsal future RPE. Concomitantly with domain specification, the eye primordium progresses from a vesicle to a cup, RPE pigmentation extends towards the ventral side, and the future ciliary body and iris form from the margin zone between RPE and retina. While much has been learned about the molecular networks controlling RPE cell specification, key questions concerning the cell proliferative parameters in RPE and the subsequent morphogenetic events still need to be addressed in greater detail.

PMID 16965267

Genetic aspects of embryonic eye development in vertebrates

Graw J. Dev Genet. 1996;18(3):181-97. Review.

The vertebrate eye comprises tissues from different embryonic origins, e.g., iris and ciliary body are derived from the wall of the diencephalon via optic vesicle and optic cup. Lens and cornea, on the other hand, come from the overlying surface ectoderm. The timely action of transcription factors and inductive signals ensure the correct development of the different eye components. Establishing the genetic basis of eye defects has been an important tool for the detailed analysis of this complex process. One of the main control genes for eye development was discovered by the analysis of the allelic series of the Small eye mouse mutants and characterized as Pax6. It is involved in the interaction between the optic cup and the overlaying ectoderm. The central role for Pax6 in eye development is conserved throughout the animal kingdom as the murine Pax6 gene induces ectopic eyes in transgenic Drosophila despite the obvious diverse organization of the eye in the fruit fly compared to vertebrates. In human, mutations in the PAX6 gene are responsible for aniridia and Peter's anomaly. In addition to Pax6, other mutations affecting the interaction of the optic cup and the lens placode have been documented in the mouse. For the differentiation of the retina from the optic cup several genes are responsible: Mi leads to microphthalmia, if mutated, and encodes for a transcription factor, which is expressed in the melanocytes of the pigmented layer of the retina. In addition, further genes are implicated in the correct development of the retina, e.g., Chx10, Dlx1, GH6, Msx1 and -2, Otx1 and -2, or Wnt7b. Mutations within the retinoblastoma gene (RB1) are responsible for retinal tumors. Knock-out mutants of RB1 exhibit a block of lens differentiation prior to the retinal defect. Besides the influence of Rb1, the lens differentiates under the influence of growth factors (e.g., FGF, IGF, PDGF, TGF), and specific genes become activated encoding cytoskeletal proteins (e.g., filensin, phakinin, vimentin), structural proteins (e.g., crystallins) or membrane proteins (e.g., Mip). The optic nerve originates from the neural retina; ganglion cells grow to the optic stalk, forming the optic nerve. Its retrograde walk to the brain through the rudiment of the optic stalk depends on the correct Pax2 expression.

PMID 8631154


Compound developmental eye disorders following inactivation of TGFbeta signaling in neural-crest stem cells

J Biol. 2005;4(3):11. Epub 2005 Dec 14.

Ittner LM, Wurdak H, Schwerdtfeger K, Kunz T, Ille F, Leveen P, Hjalt TA, Suter U, Karlsson S, Hafezi F, Born W, Sommer L. Source Research Laboratory for Calcium Metabolism, Orthopedic University Hospital Balgrist, CH-8008 Zurich, Switzerland.


BACKGROUND: Development of the eye depends partly on the periocular mesenchyme derived from the neural crest (NC), but the fate of NC cells in mammalian eye development and the signals coordinating the formation of ocular structures are poorly understood.

RESULTS: Here we reveal distinct NC contributions to both anterior and posterior mesenchymal eye structures and show that TGFbeta signaling in these cells is crucial for normal eye development. In the anterior eye, TGFbeta2 released from the lens is required for the expression of transcription factors Pitx2 and Foxc1 in the NC-derived cornea and in the chamber-angle structures of the eye that control intraocular pressure. TGFbeta enhances Foxc1 and induces Pitx2 expression in cell cultures. As in patients carrying mutations in PITX2 and FOXC1, TGFbeta signal inactivation in NC cells leads to ocular defects characteristic of the human disorder Axenfeld-Rieger's anomaly. In the posterior eye, NC cell-specific inactivation of TGFbeta signaling results in a condition reminiscent of the human disorder persistent hyperplastic primary vitreous. As a secondary effect, retinal patterning is also disturbed in mutant mice.

CONCLUSION: In the developing eye the lens acts as a TGFbeta signaling center that controls the development of eye structures derived from the NC. Defective TGFbeta signal transduction interferes with NC-cell differentiation and survival anterior to the lens and with normal tissue morphogenesis and patterning posterior to the lens. The similarity to developmental eye disorders in humans suggests that defective TGFbeta signal modulation in ocular NC derivatives contributes to the pathophysiology of these diseases.

PMID 16403239

Non-vascular smooth muscle cells in the human choroid: distribution, development and further characterization

J Anat. 2005 Oct;207(4):381-90.

May CA.

Department of Anatomy, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany. Abstract To characterize further non-vascular smooth muscle cells (NVSMC) in the choroid of the human eye, extensive morphological studies were performed including a three-dimensional distribution of NVSMC in the adult human eye and their appearance during development. Whole mounts and sections through the choroid and sclera of eyes of 42 human donors (between the 13th week of gestation and 89 years of age) were stained with antibodies against smooth muscle actin and other markers for smooth muscle cells. On the basis of their morphological localization, three groups of NVSMC could be distinguished in the adult eyes: (a) a semicircular arrangement of NVSMC in the suprachoroid and inner sclera, around the entry of posterior ciliary arteries and nerves; (b) NVSMC parallel to the vessels in the posterior eye segment between the point of entry of the posterior ciliary arteries and the point of exit of the vortex veins; and (c) a dense plaque-like arrangement of NVSMC in the suprachoroid, overlying the foveal region. The last of these groups showed most pronounced interindividual differences. During development, the first NVSMC to be observed at the 20th week of gestation belonged to group b. A complete NVSMC network was first observed in a 6-year-old donor eye. All three groups stained positive for smoothelin, caldesmon and calponin in all localizations. The NVSMC show a distinct distribution that might reflect different aspects of their function in the choroid and suprachoroid. All cells could be histochemically characterized as truly contractile.

PMID 16191166


The harderian gland: a tercentennial review

J Anat. 1994 Aug;185 ( Pt 1):1-49.

Payne AP. Source Department of Anatomy, Glasgow University, Scotland, UK.


The harderian gland was first described in 1694 by Johann Jacob Harder (1656-1711). It occurs in most terrestrial vertebrates and is located within the orbit where, in some species, it is the largest structure. It may be compound tubular or compound tubuloalveolar, and its secretory duct is usually morphologically distinct only after leaving the substance of the gland to open on the surface of the nictitating membrane. The tubules of the gland are formed of a single layer of columnar epithelial cells surrounded by myoepithelial cells. The chief product(s) of the gland varies between different groups of vertebrates, and epithelial cells possess granules or vacuoles whose contents may be mucous, serous or lipid. In rodents, the gland synthesises lipids, porphyrins and indoles. In the case of lipid vacuoles, the gland is unusual in releasing these by an exocytotic mechanism. It is unclear whether the gland can act both as an exocrine and endocrine organ. There is control of gland structure and synthesis through a variety of humoral agents, including gonadal, thyroid and pituitary hormones; in addition there is a rich autonomic innervation and many neuropeptides have been identified. The proposed functions of the gland are remarkably diverse and include the gland being (1) a source of 'saliva', (2) a site of immune response, (3) a photoprotective organ, (4) part of a retinal-pineal axis, (5) a source of pheromones, (6) a source of thermoregulatory lipids, (7) a site of osmoregulation, and (8) a source of growth factors. The gland is discussed in terms of its embryology and phylogeny, and in relation to ecological variables. Several goals of future research are identified.

PMID 7559104


Embryology of the eye and its adnexae

Dev Ophthalmol. 1992;24:1-142.

Barishak YR.

Sackler School of Medicine, University of Tel Aviv, Ramat Gan, Israel.


The embryonal and fetal development of the human eye includes a series of sequential events starting with the fertilization of the ovum and culminating in the birth of a normal baby. Three main periods can be distinguished in the prenatal development of the eye. The first period called embryogenesis is characterized by the establishment of the primary organ rudiments and ends at the end of the 3rd week with the appearance of the optic sulci on both sides of the midline at the expanded cranial end of the still open neural folds. The second period called organogenesis includes the development of the primary organ rudiments and extends till the end of the 8th week. The third period involves the differentiation of each of the primitive organs into a fully or partially active organ and is called differentiation. The period of embryogenesis is characterized by the appearance and migration of the neural crest cells and by the formation of the primary brain vesicles. The period of organogenesis extends from the 4th week till the end of the 8th week. The 4th week shows the closure of the neural canal anteriorly with the subsequent evagination of its lateral wall into optic vesicles, the invagination of the lower nasal wall of the optic vesicle causing the formation of the optic cup, and the development of the lens plate, retinal disk and embryonic fissure. The embryonic fissure extends into the optic stalk which connects the cavity of the optic vesicle with the cavity of the neural canal; the hyaloid artery penetrates into the optic cup through the embryonic fissure. During the 5th week, the optic cup is concluded, and the cells of its external layer acquire pigmentation as a result of contact with developing capillaries in the periocular mesenchyme; these capillaries anastomose with each other and form anteriorly the annular vessel. The lens plate develops into a lens pit and later into a lens vesicle which separates soon thereafter from the surface ectoderm. Inside the optic cup, the hyaloid vessels form the capillaries of the posterior tunica vasculosa lentis and through the capillaries of the lateral tunica vasculosa lentis anastomose with the annular vessel. The primary vitreous forms and the surface ectoderm overlying the lens vesicle differentiates into a primitive corneal epithelium. The facial and orbital structures also develop at this stage. The 6th week shows the incipient differentiation of the inner layer of the optic cup into a sensory retina, the formation of the secondary vitreous, the transformation of the posterior cells of the lens vesicle into primary lens fibers, the development of the periocular vasculature and the appearance of the first eyelid folds and of the anlage of the nasolacrimal duct. However, the dominating factor is the closure of the embryonic fissure.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID 1628748